Harnessing the Natural Pool of Polyketide and Non-ribosomal Peptide
Family: A Route Map towards Novel Drug Development

Aiswarya       Girija; Mallika       Vijayanathan; Sweda       Sreekumar; Jasim       Basheer; Tara   G.   Menon; Radhakrishnan   E.   Krishnankutty; Eppurathu   V.   Soniya
Abstract

The emergence of communicable and non-communicable diseases has posed a health challenge for millions of people worldwide and is a major threat to the economic and social development in the coming century. The occurrence of the recent pandemic, SARS-CoV-2, caused by lethal severe acute respiratory syndrome coronavirus 2, is one such example. Rapid research and development of drugs for the treatment and management of these diseases have become an incredibly challenging task for the pharmaceutical industry. Although, substantial attention has been paid to the discovery of therapeutic compounds from natural sources having significant medicinal potential, their synthesis has made a slow progress. Hence, the discovery of new targets by the application of the latest biotechnological and synthetic biology approaches is very much the need of the hour. Polyketides (PKs) and non-ribosomal peptides (NRPs) found in bacteria, fungi and plants are a diverse family of natural products synthesized by two classes of enzymes: polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS). These enzymes possess immense biomedical potential due to their simple architecture, catalytic capacity, as well as diversity. With the advent of the latest in-silico and in-vitro strategies, these enzymes and their related metabolic pathways, if targeted, can contribute highly towards the biosynthesis of an array of potentially natural drug leads that have antagonist effects on biopolymers associated with various human diseases. In the face of the rising threat from multidrug-resistant pathogens, this will further open new avenues for the discovery of novel and improved drugs by combining natural and synthetic approaches. This review discusses the relevance of polyketides and non-ribosomal peptides and the improvement strategies for the development of their derivatives and scaffolds, and how they will be beneficial for future bioprospecting and drug discovery.
Keywords: Polyketides, NRPS, secondary metabolites, natural products, bioactive molecules.
Graphical Abstract

[1] 
Sharma, N.; Muthamilarasan, M.; Prasad, A.; Prasad, M. Genomics approaches to synthesize plant-based biomolecules for therapeutic applications to combat SARS-CoV-2. Genomics,  2020, 112(6), 4322-4331.https://doi.org/https://doi.org/10.1016/j.ygeno.2020.07.033
[http://dx.doi.org/10.1016/j.ygeno.2020.07.033] [PMID: 32717321] 
[2] 
Glass, C.A.; Cash, J.C.; Mullen, J. Coronavirus Disease (COVID-19) https://www.who.int/emergencies/diseases/novel-coronavirus-2019Oct 12, 2020. 
[http://dx.doi.org/10.1891/9780826153425.0016b] 
[3] 
Lévesque, H.; Lafont, O. L’aspirine à Travers Les Siècles: Rappel Historique.  La Rev. Médecine Interne,  2000, 21, S8-S17.https://doi.org/https://doi.org/10.1016/S0248-8663(00)88720-2
[4] 
Du, J.; He, Z-D.; Jiang, R-W.; Ye, W-C.; Xu, H-X.; But, P.P-H. Antiviral flavonoids from the root bark of Morus alba L. Phytochemistry,  2003, 62(8), 1235-1238.https://doi.org/https://doi.org/10.1016/S0031-9422(02)00753-7
[http://dx.doi.org/10.1016/S0031-9422(02)00753-7] [PMID: 12648543] 
[5] 
Luganini, A.; Terlizzi, M.E.; Catucci, G.; Gilardi, G.; Maffei, M.E.; Gribaudo, G. The Cranberry Extract Oximacro® Exerts in vitro Virucidal Activity Against Influenza Virus by Interfering With Hemagglutinin. Front. Microbiol.,  2018, 9, 1826.
[http://dx.doi.org/10.3389/fmicb.2018.01826] [PMID: 30131793] 
[6] 
Wangchuk, P. Therapeutic Applications of Natural Products in Herbal Medicines, Biodiscovery Programs, and Biomedicine. J. Biol. Act. Prod. from Nat.,  2018, 8(1), 1-20.
[http://dx.doi.org/10.1080/22311866.2018.1426495] 
[7] 
Beutler, J. A. Natural Products as a Foundation for Drug Discovery.  Curr. Protoc. Pharmacol,  2009, 46, 9.11.1-9.11.21.
[http://dx.doi.org/10.1002/0471141755.ph0911s46] 
[8] 
Chávez-Hernández, A.L.; Sánchez-Cruz, N.; Medina-Franco, J.L. Fragment Library of Natural Products and Compound Databases for Drug Discovery. Biomolecules,  2020, 10(11), 1-16.
[http://dx.doi.org/10.3390/biom10111518] [PMID: 33172012] 
[9] 
Medina-Franco, J.L.; Saldívar-González, F.I. Cheminformatics to Characterize Pharmacologically Active Natural Products. Biomolecules,  2020, 10(11), 1-14.
[http://dx.doi.org/10.3390/biom10111566] [PMID: 33213003] 
[10] 
Lautié, E.; Russo, O.; Ducrot, P.; Boutin, J.A. Unraveling Plant Natural Chemical Diversity for Drug Discovery Purposes. Front. Pharmacol.,  2020, 11, 397.
[http://dx.doi.org/10.3389/fphar.2020.00397] [PMID: 32317969] 
[11] 
Magiorakos, A.P.; Srinivasan, A.; Carey, R.B.; Carmeli, Y.; Falagas, M.E.; Giske, C.G.; Harbarth, S.; Hindler, J.F.; Kahlmeter, G.; Olsson-Liljequist, B.; Paterson, D.L.; Rice, L.B.; Stelling, J.; Struelens, M.J.; Vatopoulos, A.; Weber, J.T.; Monnet, D.L. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin. Microbiol. Infect.,  2012, 18(3), 268-281.
[http://dx.doi.org/10.1111/j.1469-0691.2011.03570.x] [PMID: 21793988] 
[12] 
Silver, L.L. Natural products as a source of drug leads to overcome drug resistance. Future Microbiol.,  2015, 10(11), 1711-1718.
[http://dx.doi.org/10.2217/fmb.15.67] [PMID: 26517443] 
[13] 
Keyvani-Ghamsari, S.; Khorsandi, K.; Gul, A. Curcumin effect on cancer cells' multidrug resistance: An update. Phytotherapy Research.,  2020, 34, 2534-2556.
[http://dx.doi.org/10.1002/ptr.6703] [PMID: 32307747] 
[14] 
Waugh, A.C.W.; Long, P.F. Prospects for generating new antibiotics. Sci. Prog.,  2002, 85(Pt 1), 73-88.
[http://dx.doi.org/10.3184/003685002783238915] [PMID: 11969120] 
[15] 
Agrawal, S.; Acharya, D.; Adholeya, A.; Barrow, C. J.; Deshmukh, S. K. Nonribosomal Peptides from Marine Microbes and Their Antimicrobial and Anticancer Potential.  Frontiers in Pharmacology. Frontiers Media S.A.,  2017 2. November;, 828.
[http://dx.doi.org/10.3389/fphar.2017.00828] 
[16] 
Kumar, P.; Kizhakkedathu, J.N.; Straus, S.K. Antimicrobial Peptides: Diversity, Mechanism of Action and Strategies to Improve the Activity and Biocompatibility In Vivo. Biomolecules,  2018, 8(1), E4.
[http://dx.doi.org/10.3390/biom8010004] [PMID: 29351202] 
[17] 
Jasim, B.; Mathew, J.; Radhakrishnan, E.K. Identification of a novel endophytic Bacillus sp. from Capsicum annuum with highly efficient and broad spectrum plant probiotic effect. J. Appl. Microbiol.,  2016, 121(4), 1079-1094.
[http://dx.doi.org/10.1111/jam.13214] [PMID: 27359249] 
[18] 
Alberto Martínez-Núñez, M.; López, Y Nonribosomal Peptides Synthetases and Their Applications in Industry.  Sustain. Chem. Process, 2016.
[http://dx.doi.org/10.1186/s40508-016-0057-6] 
[19] 
Lin, S-C.; Ho, C-T.; Chuo, W-H.; Li, S.; Wang, T.T.; Lin, C-C. Effective inhibition of MERS-CoV infection by resveratrol. BMC Infect. Dis.,  2017, 17(1), 144.
[http://dx.doi.org/10.1186/s12879-017-2253-8] [PMID: 28193191] 
[20] 
Caly, L.; Druce, J.D.; Catton, M.G.; Jans, D.A.; Wagstaff, K.M. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res.,  2020, 178, 104787.https://doi.org/https://doi.org/10.1016/j.antiviral.2020.104787
[http://dx.doi.org/10.1016/j.antiviral.2020.104787] [PMID: 32251768] 
[21] 
Gaisser, S.; Kellenberger, L.; Kaja, A.L.; Weston, A.J.; Lill, R.E.; Wirtz, G.; Kendrew, S.G.; Low, L.; Sheridan, R.M.; Wilkinson, B.; Galloway, I.S.; Stutzman-Engwall, K.; McArthur, H.A.; Staunton, J.; Leadlay, P.F. Direct production of ivermectin-like drugs after domain exchange in the avermectin polyketide synthase of Streptomyces avermitilis ATCC31272. Org. Biomol. Chem.,  2003, 1(16), 2840-2847.
[http://dx.doi.org/10.1039/b304022d] [PMID: 12968333] 
[22] 
Liu, H.; Ye, F.; Sun, Q.; Liang, H.; Li, C.; Lu, R.; Huang, B.; Tan, W.; Lai, L. Scutellaria Baicalensis Extract and Baicalein Inhibit Replication of SARS-CoV-2 and Its 3C-like Protease in vitro. bioRxiv, 2020.
[http://dx.doi.org/10.1101/2020.04.10.035824] 
[23] 
Ngwa, W.; Kumar, R.; Thompson, D.; Lyerly, W.; Moore, R.; Reid, T-E.; Lowe, H.; Toyang, N. Potential of Flavonoid-Inspired Phytomedicines against COVID-19. Molecules,  2020, 25(11), 2707.
[http://dx.doi.org/10.3390/molecules25112707] [PMID: 32545268] 
[24] 
Suwannarach, N.; Kumla, J.; Sujarit, K.; Pattananandecha, T.; Saenjum, C.; Lumyong, S. Natural Bioactive Compounds from Fungi as Potential Candidates for Protease Inhibitors and Immunomodulators to Apply for Coronaviruses. Molecules,  2020, 25(8), 1800.
[http://dx.doi.org/10.3390/molecules25081800] [PMID: 32295300] 
[25] 
Pluskal, T.; Torrens-Spence, M.P.; Fallon, T.R.; De Abreu, A.; Shi, C.H.; Weng, J-K. The biosynthetic origin of psychoactive kavalactones in kava. Nat. Plants,  2019, 5(8), 867-878.
[http://dx.doi.org/10.1038/s41477-019-0474-0] [PMID: 31332312] 
[26] 
Katsuyama, Y.; Kita, T.; Funa, N.; Horinouchi, S. Curcuminoid biosynthesis by two type III polyketide synthases in the herb Curcuma longa. J. Biol. Chem.,  2009, 284(17), 11160-11170.
[http://dx.doi.org/10.1074/jbc.M900070200] [PMID: 19258320] 
[27] 
Cane, D.E.; Walsh, C.T.; Khosla, C. Harnessing the biosynthetic code: combinations, permutations, and mutations. Science,  1998, 282(5386), 63-68.
[http://dx.doi.org/10.1126/science.282.5386.63] [PMID: 9756477] 
[28] 
Gallo, A.; Ferrara, M.; Perrone, G. Phylogenetic study of polyketide synthases and nonribosomal peptide synthetases involved in the biosynthesis of mycotoxins. Toxins (Basel),  2013, 5(4), 717-742.
[http://dx.doi.org/10.3390/toxins5040717] [PMID: 23604065] 
[29] 
Tang, S.; Zhang, W.; Li, Z.; Li, H.; Geng, C.; Huang, X.; Lu, X. Discovery and Characterization of a PKS-NRPS Hybrid in Aspergillus terreus by Genome Mining. J. Nat. Prod.,  2020, 83(2), 473-480.
[http://dx.doi.org/10.1021/acs.jnatprod.9b01140] [PMID: 32077283] 
[30] 
Castoe, T.A.; Stephens, T.; Noonan, B.P.; Calestani, C. A novel group of type I polyketide synthases (PKS) in animals and the complex phylogenomics of PKSs. Gene,  2007, 392(1-2), 47-58.https://doi.org/https://doi.org/10.1016/j.gene.2006.11.005
[http://dx.doi.org/10.1016/j.gene.2006.11.005] [PMID: 17207587] 
[31] 
Shimizu, Y.; Ogata, H.; Goto, S. Discriminating the reaction types of plant type III polyketide synthases. Bioinformatics,  2017, 33(13), 1937-1943.
[http://dx.doi.org/10.1093/bioinformatics/btx112] [PMID: 28334262] 
[32] 
Mapook, A.; Macabeo, A.P.G.; Thongbai, B.; Hyde, K.D.; Stadler, M. Polyketide-Derived Secondary Metabolites from a Dothideomycetes Fungus, Pseudopalawania siamensisgen. et sp. nov., (Muyocopronales) with Antimicrobial and Cytotoxic Activities. Biomolecules,  2020, 10(4), 569.
[http://dx.doi.org/10.3390/biom10040569] [PMID: 32276418] 
[33] 
Xie, L.; Liu, P.; Zhu, Z.; Zhang, S.; Zhang, S.; Li, F.; Zhang, H.; Li, G.; Wei, Y.; Sun, R. Phylogeny and Expression Analyses Reveal Important Roles for Plant PKS III Family during the Conquest of Land by Plants and Angiosperm Diversification. Front. Plant Sci.,  2016, 7, 1312.
[http://dx.doi.org/10.3389/fpls.2016.01312] [PMID: 27625671] 
[34] 
Sabatini, M.; Comba, S.; Altabe, S.; Recio-Balsells, A.I.; Labadie, G.R.; Takano, E.; Gramajo, H.; Arabolaza, A. Biochemical characterization of the minimal domains of an iterative eukaryotic polyketide synthase. FEBS J.,  2018, 285(23), 4494-4511.
[http://dx.doi.org/10.1111/febs.14675] [PMID: 30300504] 
[35] 
Calestani, C.; Rast, J. P.; Davidson, E. H. Isolation of Pigment Cell Specific Genes in the Sea Urchin Embryo by Differential Macroarray Screening.  Development,  2003, 130(19), 4587-4596.
[http://dx.doi.org/10.1242/dev.00647] 
[36] 
Calestani, C.; Wessel, G.M. These Colors Don’t Run: Regulation of Pigment-Biosynthesis in Echinoderms. Results Probl. Cell Differ.,  2018, 65, 515-525.
[http://dx.doi.org/10.1007/978-3-319-92486-1_22] [PMID: 30083933] 
[37] 
Hojo, M.; Omi, A.; Hamanaka, G.; Shindo, K.; Shimada, A.; Kondo, M.; Narita, T.; Kiyomoto, M.; Katsuyama, Y.; Ohnishi, Y.; Irie, N.; Takeda, H. Unexpected link between polyketide synthase and calcium carbonate biomineralization. Zoological Lett.,  2015, 1, 3.
[http://dx.doi.org/10.1186/s40851-014-0001-0] [PMID: 26605048] 
[38] 
Shou, Q.; Feng, L.; Long, Y.; Han, J.; Nunnery, J.K.; Powell, D.H.; Butcher, R.A. A hybrid polyketide-nonribosomal peptide in nematodes that promotes larval survival. Nat. Chem. Biol.,  2016, 12(10), 770-772.
[http://dx.doi.org/10.1038/nchembio.2144] [PMID: 27501395] 
[39] 
Cooke, T.F.; Fischer, C.R.; Wu, P.; Jiang, T-X.; Xie, K.T.; Kuo, J.; Doctorov, E.; Zehnder, A.; Khosla, C.; Chuong, C-M.; Bustamante, C.D. Genetic Mapping and Biochemical Basis of Yellow Feather Pigmentation in Budgerigars. Cell,  2017, 171(2), 427-439.e21.
[http://dx.doi.org/10.1016/j.cell.2017.08.016] [PMID: 28985565] 
[40] 
Collie, N.; Myers, W.S. VII.—The Formation of Orcinol and Other Condensation Products from Dehydracetic Acid. J. Chem. Soc. Trans.,  1893, 63(0), 122-128.
[http://dx.doi.org/10.1039/CT8936300122] 
[41] 
Birch, A.J.; Donovan, F.W.; Moewus, F. Biogenesis of flavonoids in Chlamydomonas eugametos. Nature,  1953, 172(4385), 902-904.
[http://dx.doi.org/10.1038/172902a0] [PMID: 13111225] 
[42] 
Hutchinson, C.R. Microbial polyketide synthases: more and more prolific. Proc. Natl. Acad. Sci. USA,  1999, 96(7), 3336-3338.
[http://dx.doi.org/10.1073/pnas.96.7.3336] [PMID: 10097038] 
[43] 
Olano, C. Hutchinson’s legacy: keeping on polyketide biosynthesis. J. Antibiot. (Tokyo),  2011, 64(1), 51-57.
[http://dx.doi.org/10.1038/ja.2010.126] [PMID: 21063423] 
[44] 
Wang, J.; Zhang, R.; Chen, X.; Sun, X.; Yan, Y.; Shen, X.; Yuan, Q. Biosynthesis of aromatic polyketides in microorganisms using type II polyketide synthases. Microb. Cell Fact.,  2020, 19(1), 110.
[http://dx.doi.org/10.1186/s12934-020-01367-4] [PMID: 32448179] 
[45] 
Bystrykh, L.V.; Fernández-Moreno, M.A.; Herrema, J.K.; Malpartida, F.; Hopwood, D.A.; Dijkhuizen, L. Production of actinorhodin-related “blue pigments” by Streptomyces coelicolor A3(2). J. Bacteriol.,  1996, 178(8), 2238-2244.
[http://dx.doi.org/10.1128/JB.178.8.2238-2244.1996] [PMID: 8636024] 
[46] 
Goss, R.J.M.; Shankar, S.; Fayad, A.A. The Generation of “UnNatural” Products: Synthetic Biology Meets Synthetic Chemistry. Natural Product Reports; Royal Society of Chemistry, 2012, pp. 870-889.
[47] 
Tsai, S-C.S.; Ames, B.D. Structural enzymology of polyketide synthases. Methods Enzymol.,  2009, 459, 17-47.
[http://dx.doi.org/10.1016/S0076-6879(09)04602-3] [PMID: 19362634] 
[48] 
Korman, T.P.; Ames, B. (Sheryl) Tsai, S.-C. 1.08 - Structural Enzymology of Polyketide Synthase: The Structure–Sequence–Function Correlation; Liu, H.-W. (Ben); Mander, L. B. T.-C. N. P. I. I., Eds.; Elsevier: Oxford, 2010, pp. 305-345.
[http://dx.doi.org/10.1016/B978-008045382-8.00020-4] 
[49] 
Risdian, C.; Mozef, T.; Wink, J. Biosynthesis of Polyketides in Streptomyces. Microorganisms,  2019, 7(5), 124.
[http://dx.doi.org/10.3390/microorganisms7050124] [PMID: 31064143] 
[50] 
Smith, S.; Tsai, S.C. The type I fatty acid and polyketide synthases: a tale of two megasynthases. Nat. Prod. Rep.,  2007, 24(5), 1041-1072.
[http://dx.doi.org/10.1039/b603600g] [PMID: 17898897] 
[51] 
Cheng, Y-Q.; Coughlin, J.M.; Lim, S-K.; Shen, B.; Type, I. Type I polyketide synthases that require discrete acyltransferases. Methods Enzymol.,  2009, 459, 165-186.
[http://dx.doi.org/10.1016/S0076-6879(09)04608-4] [PMID: 19362640] 
[52] 
Castonguay, R.; Valenzano, C.R.; Chen, A.Y.; Keatinge-Clay, A.; Khosla, C.; Cane, D.E. Stereospecificity of ketoreductase domains 1 and 2 of the tylactone modular polyketide synthase. J. Am. Chem. Soc.,  2008, 130(35), 11598-11599.
[http://dx.doi.org/10.1021/ja804453p] [PMID: 18693734] 
[53] 
Chen, A.Y.; Schnarr, N.A.; Kim, C-Y.; Cane, D.E.; Khosla, C. Extender unit and acyl carrier protein specificity of ketosynthase domains of the 6-deoxyerythronolide B synthase. J. Am. Chem. Soc.,  2006, 128(9), 3067-3074.
[http://dx.doi.org/10.1021/ja058093d] [PMID: 16506788] 
[54] 
Staunton, J.; Weissman, K.J. Polyketide biosynthesis: a millennium review. Nat. Prod. Rep.,  2001, 18(4), 380-416.
[http://dx.doi.org/10.1039/a909079g] [PMID: 11548049] 
[55] 
Szu, P-H.; Govindarajan, S.; Meehan, M.J.; Das, A.; Nguyen, D.D.; Dorrestein, P.C.; Minshull, J.; Khosla, C. Analysis of the ketosynthase-chain length factor heterodimer from the fredericamycin polyketide synthase. Chem. Biol.,  2011, 18(8), 1021-1031.
[http://dx.doi.org/10.1016/j.chembiol.2011.07.015] [PMID: 21867917] 
[56] 
Castaldo, G.; Zucko, J.; Heidelberger, S.; Vujaklija, D.; Hranueli, D.; Cullum, J.; Wattana-Amorn, P.; Crump, M.P.; Crosby, J.; Long, P.F. Proposed arrangement of proteins forming a bacterial type II polyketide synthase. Chem. Biol.,  2008, 15(11), 1156-1165.https://doi.org/https://doi.org/10.1016/j.chembiol.2008.09.010
[http://dx.doi.org/10.1016/j.chembiol.2008.09.010] [PMID: 19022176] 
[57] 
Zhan, J.; Watanabe, K.; Tang, Y. Synergistic actions of a monooxygenase and cyclases in aromatic polyketide biosynthesis. ChemBioChem,  2008, 9(11), 1710-1715.
[http://dx.doi.org/10.1002/cbic.200800178] [PMID: 18604835] 
[58] 
Dhakal, D.; Lim, S-K.; Kim, D.H.; Kim, B-G.; Yamaguchi, T.; Sohng, J.K. Complete genome sequence of Streptomyces peucetius ATCC 27952, the producer of anticancer anthracyclines and diverse secondary metabolites. J. Biotechnol.,  2018, 267, 50-54.https://doi.org/https://doi.org/10.1016/j.jbiotec.2017.12.024
[http://dx.doi.org/10.1016/j.jbiotec.2017.12.024] [PMID: 29307836] 
[59] 
Dao, T.T.H.; Linthorst, H.J.M.; Verpoorte, R. Chalcone synthase and its functions in plant resistance. Phytochem. Rev.,  2011, 10(3), 397-412.
[http://dx.doi.org/10.1007/s11101-011-9211-7] [PMID: 21909286] 
[60] 
Austin, M.B.; Noel, J.P.; Zhan, J.; Watanabe, K.; Tang, Y.; Muir, S.R.; Collins, G.J.; Robinson, S.; Hughes, S.; Bovy, A. POLYKETIDE SYNTHASE GENE MANIPULATION: A Structure-Function Approach in Engineering Novel Antibiotics. Trends Plant Sci.,  2003, 9(2), 201-238.
[http://dx.doi.org/10.1038/88150] 
[61] 
Abe, I.; Morita, H. Structure and function of the chalcone synthase superfamily of plant type III polyketide synthases. Nat. Prod. Rep.,  2010, 27(6), 809-838.
[http://dx.doi.org/10.1039/b909988n] [PMID: 20358127] 
[62] 
Lim, Y.P.; Go, M.K.; Yew, W.S. Exploiting the Biosynthetic Potential of Type III Polyketide Synthases. Molecules,  2016, 21(6), 806.
[http://dx.doi.org/10.3390/molecules21060806] [PMID: 27338328] 
[63] 
Naake, T.; Maeda, H. A.; Proost, S.; Tohge, T.; Fernie, A. R. Kingdom-Wide Analysis of the Evolution of the Plant Type III Polyketide Synthase Superfamily.  bioRxiv, 2020.
[http://dx.doi.org/10.1101/2020.04.28.059733] 
[64] 
Navarro-Muñoz, J.C.; Collemare, J. Evolutionary Histories of Type III Polyketide Synthases in Fungi. Front. Microbiol.,  2020, 10, 3018.
[http://dx.doi.org/10.3389/fmicb.2019.03018] [PMID: 32038517] 
[65] 
Jeya, M.; Kim, T.S.; Tiwari, M.K.; Li, J.; Zhao, H.; Lee, J.K. The Botrytis cinerea type III polyketide synthase shows unprecedented high catalytic efficiency toward long chain acyl-CoAs. Mol. Biosyst.,  2012, 8(11), 2864-2867.
[http://dx.doi.org/10.1039/c2mb25282a] [PMID: 22945364] 
[66] 
Conway, K.R.; Boddy, C.N. ClusterMine360: a database of microbial PKS/NRPS biosynthesis. Nucleic Acids Res.,  2013, 41(Database issue), D402-D407.
[http://dx.doi.org/10.1093/nar/gks993] [PMID: 23104377] 
[67] 
Khater, S.; Gupta, M.; Agrawal, P.; Sain, N.; Prava, J.; Gupta, P.; Grover, M.; Kumar, N.; Mohanty, D. SBSPKSv2: structure-based sequence analysis of polyketide synthases and non-ribosomal peptide synthetases. Nucleic Acids Res.,  2017, 45(W1), W72-W79.
[http://dx.doi.org/10.1093/nar/gkx344] [PMID: 28460065] 
[68] 
Austin, M.B.; Izumikawa, M.; Bowman, M.E.; Udwary, D.W.; Ferrer, J-L.; Moore, B.S.; Noel, J.P. Crystal structure of a bacterial type III polyketide synthase and enzymatic control of reactive polyketide intermediates. J. Biol. Chem.,  2004, 279(43), 45162-45174.
[http://dx.doi.org/10.1074/jbc.M406567200] [PMID: 15265863] 
[69] 
Zhu, X.; Zhang, W. Tagging polyketides/non-ribosomal peptides with a clickable functionality and applications. Front Chem.,  2015, 3, 11.
[http://dx.doi.org/10.3389/fchem.2015.00011] [PMID: 25815285] 
[70] 
Felnagle, E.A.; Jackson, E.E.; Chan, Y.A.; Podevels, A.M.; Berti, A.D.; McMahon, M.D.; Thomas, M.G. Nonribosomal peptide synthetases involved in the production of medically relevant natural products. Mol. Pharm.,  2008, 5(2), 191-211.
[http://dx.doi.org/10.1021/mp700137g] [PMID: 18217713] 
[71] 
Agrawal, S.; Adholeya, A.; Deshmukh, S. K. The Pharmacological Potential of Non-Ribosomal Peptides from Marine Sponge and Tunicates.  Frontiers in Pharmacology. Frontiers Media S.A,  2016 25. October;, 333.
[72] 
Mach, B.; Reich, E.; Tatum, E. L. SEPARATION OF THE BIOSYNTHESIS OF THE ANTIBIOTIC POLYPEPTIDE TYROCIDINE FROM PROTEIN BIOSYNTHESIS.  Proc. Natl. Acad. Sci,  1963, 50(1), 175-181.
[73] 
Mankelow, D.P.; Neilan, B.A. Non-Ribosomal Peptide Antibiotics. Expert Opinion on Therapeutic Patents; Ashley Publications Ltd, 2000, pp. 1583-1591.
[74] 
Mootz, H. D.; Schwarzer, D.; Marahiel, M. A. Ways of Assembling Complex Natural Products on Modular Nonribosomal Peptide Synthetases. ChemBioChem; John Wiley & Sons, Ltd, 2002, pp. 3. June;490-504.
[http://dx.doi.org/10.1002/1439-7633(20020603)3:6490::AID-CBIC4903.0.CO;2-N] 
[75] 
Bloudoff, K.; Fage, C. D.; Marahiel, M. A.; Schmeing, T. M. Structural and Mutational Analysis of the Nonribosomal Peptide Synthetase Heterocyclization Domain Provides Insight into Catalysis.  Proc. Natl. Acad. Sci.,  2017, 114(1), 95-100.
[http://dx.doi.org/10.1073/pnas.1614191114] 
[76] 
Walsh, C.T. The chemical versatility of natural-product assembly lines. Acc. Chem. Res.,  2008, 41(1), 4-10.
[http://dx.doi.org/10.1021/ar7000414] [PMID: 17506516] 
[77] 
Miller, B.R.; Gulick, A.M. Structural Biology of Nonribosomal Peptide Synthetases. Methods Mol. Biol.,  2016, 1401, 3-29.
[http://dx.doi.org/10.1007/978-1-4939-3375-4_1] [PMID: 26831698] 
[78] 
Wei, Y.; Zhang, L.; Zhou, Z.; Yan, X. Diversity of Gene Clusters for Polyketide and Nonribosomal Peptide Biosynthesis Revealed by Metagenomic Analysis of the Yellow Sea Sediment. Front. Microbiol.,  2018, 9, 295.
[http://dx.doi.org/10.3389/fmicb.2018.00295] [PMID: 29535686] 
[79] 
Owen, J.G.; Calcott, M.J.; Robins, K.J.; Ackerley, D.F. Generating Functional Recombinant NRPS Enzymes in the Laboratory Setting via Peptidyl Carrier Protein Engineering. Cell Chem. Biol.,  2016, 23(11), 1395-1406.https://doi.org/https://doi.org/10.1016/j.chembiol.2016.09.014
[http://dx.doi.org/10.1016/j.chembiol.2016.09.014] [PMID: 27984027] 
[80] 
Drake, E.J.; Miller, B.R.; Shi, C.; Tarrasch, J.T.; Sundlov, J.A.; Allen, C.L.; Skiniotis, G.; Aldrich, C.C.; Gulick, A.M. Structures of two distinct conformations of holo-non-ribosomal peptide synthetases. Nature,  2016, 529(7585), 235-238.
[http://dx.doi.org/10.1038/nature16163] [PMID: 26762461] 
[81] 
Bloudoff, K.; Schmeing, T. M. Structural and Functional Aspects of the Nonribosomal Peptide Synthetase Condensation Domain Superfamily: Discovery, Dissection and Diversity. Biochimica et Biophysica Acta - Proteins and Proteomics.,  2017 1. November;, 1587-1604.
[http://dx.doi.org/10.1016/j.bbapap.2017.05.010] 
[82] 
Lambalot, R.H.; Gehring, A.M.; Flugel, R.S.; Zuber, P.; LaCelle, M.; Marahiel, M.A.; Reid, R.; Khosla, C.; Walsh, C.T. A new enzyme superfamily - the phosphopantetheinyl transferases. Chem. Biol.,  1996, 3(11), 923-936.
[http://dx.doi.org/10.1016/S1074-5521(96)90181-7] [PMID: 8939709] 
[83] 
Boot, C.M.; Gassner, N.C.; Compton, J.E.; Tenney, K.; Tamble, C.M.; Lokey, R.S.; Holman, T.R.; Crews, P. Pinpointing pseurotins from a marine-derived Aspergillus as tools for chemical genetics using a synthetic lethality yeast screen. J. Nat. Prod.,  2007, 70(10), 1672-1675.
[http://dx.doi.org/10.1021/np070307c] [PMID: 17929896] 
[84] 
Kim, M.Y.; Sohn, J.H.; Ahn, J.S.; Oh, H. Alternaramide, a cyclic depsipeptide from the marine-derived fungus Alternaria sp. SF-5016. J. Nat. Prod.,  2009, 72(11), 2065-2068.
[http://dx.doi.org/10.1021/np900464p] [PMID: 19943624] 
[85] 
Luesch, H.; Yoshida, W.Y.; Moore, R.E.; Paul, V.J.; Corbett, T.H. Total structure determination of apratoxin A, a potent novel cytotoxin from the marine cyanobacterium Lyngbya majuscula. J. Am. Chem. Soc.,  2001, 123(23), 5418-5423.
[http://dx.doi.org/10.1021/ja010453j] [PMID: 11389621] 
[86] 
Gutiérrez, M.; Suyama, T.L.; Engene, N.; Wingerd, J.S.; Matainaho, T.; Gerwick, W.H. Apratoxin D, a potent cytotoxic cyclodepsipeptide from papua new guinea collections of the marine cyanobacteria Lyngbya majuscula and Lyngbya sordida. J. Nat. Prod.,  2008, 71(6), 1099-1103.
[http://dx.doi.org/10.1021/np800121a] [PMID: 18444683] 
[87] 
Matthew, S.; Schupp, P.J.; Luesch, H. Apratoxin E, a cytotoxic peptolide from a guamanian collection of the marine cyanobacterium Lyngbya bouillonii. J. Nat. Prod.,  2008, 71(6), 1113-1116.
[http://dx.doi.org/10.1021/np700717s] [PMID: 18461997] 
[88] 
Pettit, G.R.; Knight, J.C.; Herald, D.L.; Pettit, R.K.; Hogan, F.; Mukku, V.J.R.V.; Hamblin, J.S.; Dodson, M.J.; Chapuis, J-C. Antineoplastic agents. 570. Isolation and structure elucidation of bacillistatins 1 and 2 from a marine Bacillus silvestris. J. Nat. Prod.,  2009, 72(3), 366-371.
[http://dx.doi.org/10.1021/np800603u] [PMID: 19226154] 
[89] 
Asolkar, R.N.; Freel, K.C.; Jensen, P.R.; Fenical, W.; Kondratyuk, T.P.; Park, E.J.; Pezzuto, J.M. Arenamides A-C, cytotoxic NFkappaB inhibitors from the marine actinomycete Salinispora arenicola. J. Nat. Prod.,  2009, 72(3), 396-402.
[http://dx.doi.org/10.1021/np800617a] [PMID: 19117399] 
[90] 
Oku, N.; Adachi, K.; Matsuda, S.; Kasai, H.; Takatsuki, A.; Shizuri, Y. Ariakemicins A and B, novel polyketide-peptide antibiotics from a marine gliding bacterium of the genus Rapidithrix. Org. Lett.,  2008, 10(12), 2481-2484.
[http://dx.doi.org/10.1021/ol8007292] [PMID: 18498148] 
[91] 
He, F.; Bao, J.; Zhang, X.Y.; Tu, Z.C.; Shi, Y.M.; Qi, S.H. Asperterrestide A, a cytotoxic cyclic tetrapeptide from the marine-derived fungus Aspergillus terreus SCSGAF0162. J. Nat. Prod.,  2013, 76(6), 1182-1186.
[http://dx.doi.org/10.1021/np300897v] [PMID: 23806112] 
[92] 
Han, B.; Gross, H.; Goeger, D.E.; Mooberry, S.L.; Gerwick, W.H. Aurilides B and C, cancer cell toxins from a Papua New Guinea collection of the marine cyanobacterium Lyngbya majuscula. J. Nat. Prod.,  2006, 69(4), 572-575.
[http://dx.doi.org/10.1021/np0503911] [PMID: 16643028] 
[93] 
Simmons, T.L.; McPhail, K.L.; Ortega-Barría, E.; Mooberry, S.L.; Gerwick, W.H. Belamide A, a New Antimitotic Tetrapeptide from a Panamanian Marine Cyanobacterium. Tetrahedron Lett.,  2006, 47(20), 3387-3390.https://doi.org/https://doi.org/10.1016/j.tetlet.2006.03.082
[http://dx.doi.org/10.1016/j.tetlet.2006.03.082] 
[94] 
Teruya, T.; Sasaki, H.; Fukazawa, H.; Suenaga, K. Bisebromoamide, a potent cytotoxic peptide from the marine cyanobacterium Lyngbya sp.: isolation, stereostructure, and biological activity. Org. Lett.,  2009, 11(21), 5062-5065.
[http://dx.doi.org/10.1021/ol9020546] [PMID: 19803465] 
[95] 
Barsby, T.; Kelly, M.T.; Gagné, S.M.; Andersen, R.J.; Bogorol, A. Bogorol A produced in culture by a marine Bacillus sp. reveals a novel template for cationic peptide antibiotics. Org. Lett.,  2001, 3(3), 437-440.
[http://dx.doi.org/10.1021/ol006942q] [PMID: 11428033] 
[96] 
Tan, L.T.; Okino, T.; Gerwick, W.H. Bouillonamide: a mixed polyketide-peptide cytotoxin from the marine cyanobacterium Moorea bouillonii. Mar. Drugs,  2013, 11(8), 3015-3024.
[http://dx.doi.org/10.3390/md11083015] [PMID: 23966034] 
[97] 
Speitling, M.; Smetanina, O.F.; Kuznetsova, T.A.; Laatsch, H. Bromoalterochromides A and A′, unprecedented chromopeptides from a marine Pseudoalteromonas maricaloris strain KMM 636T. J. Antibiot. (Tokyo),  2007, 60(1), 36-42.
[http://dx.doi.org/10.1038/ja.2007.5] [PMID: 17390587] 
[98] 
Müller, D.; Krick, A.; Kehraus, S.; Mehner, C.; Hart, M.; Küpper, F.C.; Saxena, K.; Prinz, H.; Schwalbe, H.; Janning, P.; Waldmann, H.; König, G.M. Brunsvicamides A-C: sponge-related cyanobacterial peptides with Mycobacterium tuberculosis protein tyrosine phosphatase inhibitory activity. J. Med. Chem.,  2006, 49(16), 4871-4878.
[http://dx.doi.org/10.1021/jm060327w] [PMID: 16884299] 
[99] 
Pesic, A.; Baumann, H.I.; Kleinschmidt, K.; Ensle, P.; Wiese, J.; Süssmuth, R.D.; Imhoff, J.F. Champacyclin, a new cyclic octapeptide from Streptomyces strain C42 isolated from the Baltic Sea. Mar. Drugs,  2013, 11(12), 4834-4857.
[http://dx.doi.org/10.3390/md11124834] [PMID: 24317473] 
[100] 
Jiang, W.; Ye, P.; Chen, C.T.A.; Wang, K.; Liu, P.; He, S.; Wu, X.; Gan, L.; Ye, Y.; Wu, B. Two novel hepatocellular carcinoma cycle inhibitory cyclodepsipeptides from a hydrothermal vent crab-associated fungus Aspergillus clavatus C2WU. Mar. Drugs,  2013, 11(12), 4761-4772.
[http://dx.doi.org/10.3390/md11124761] [PMID: 24317468] 
[101] 
Medina, R.A.; Goeger, D.E.; Hills, P.; Mooberry, S.L.; Huang, N.; Romero, L.I.; Ortega-Barría, E.; Gerwick, W.H.; McPhail, K.L. Coibamide A, a potent antiproliferative cyclic depsipeptide from the Panamanian marine cyanobacterium Leptolyngbya sp. J. Am. Chem. Soc.,  2008, 130(20), 6324-6325.
[http://dx.doi.org/10.1021/ja801383f] [PMID: 18444611] 
[102] 
Chen, Z.; Song, Y.; Chen, Y.; Huang, H.; Zhang, W.; Ju, J. Cyclic heptapeptides, cordyheptapeptides C-E, from the marine-derived fungus Acremonium persicinum SCSIO 115 and their cytotoxic activities. J. Nat. Prod.,  2012, 75(6), 1215-1219.
[http://dx.doi.org/10.1021/np300152d] [PMID: 22642609] 
[103] 
Fremlin, L.J.; Piggott, A.M.; Lacey, E.; Capon, R.J. Cottoquinazoline A and cotteslosins A and B, metabolites from an Australian marine-derived strain of Aspergillus versicolor. J. Nat. Prod.,  2009, 72(4), 666-670.
[http://dx.doi.org/10.1021/np800777f] [PMID: 19245260] 
[104] 
Mitova, M.; Popov, S.; De Rosa, S. Cyclic peptides from a Ruegeria strain of bacteria associated with the sponge Suberites domuncula. J. Nat. Prod.,  2004, 67(7), 1178-1181.
[http://dx.doi.org/10.1021/np049900+] [PMID: 15270577] 
[105] 
Montaser, R.; Abboud, K.A.; Paul, V.J.; Luesch, H. Pitiprolamide, a proline-rich dolastatin 16 analogue from the marine cyanobacterium Lyngbya majuscula from Guam. J. Nat. Prod.,  2011, 74(1), 109-112.
[http://dx.doi.org/10.1021/np1006839] [PMID: 21138309] 
[106] 
Meickle, T.; Matthew, S.; Ross, C.; Luesch, H.; Paul, V. Bioassay-guided isolation and identification of desacetylmicrocolin B from Lyngbya cf. polychroa. Planta Med.,  2009, 75(13), 1427-1430.
[http://dx.doi.org/10.1055/s-0029-1185675] [PMID: 19431099] 
[107] 
Simmons, T.L.; Nogle, L.M.; Media, J.; Valeriote, F.A.; Mooberry, S.L.; Gerwick, W.H. Desmethoxymajusculamide C, a cyanobacterial depsipeptide with potent cytotoxicity in both cyclic and ring-opened forms. J. Nat. Prod.,  2009, 72(6), 1011-1016.
[http://dx.doi.org/10.1021/np9001674] [PMID: 19489598] 
[108] 
Gunasekera, S.P.; Ross, C.; Paul, V.J.; Matthew, S.; Luesch, H. Dragonamides C and D, linear lipopeptides from the marine cyanobacterium brown Lyngbya polychroa. J. Nat. Prod.,  2008, 71(5), 887-890.
[http://dx.doi.org/10.1021/np0706769] [PMID: 18393465] 
[109] 
Hayakawa, Y.; Hattori, Y.; Kawasaki, T.; Kanoh, K.; Adachi, K.; Shizuri, Y.; Shin-ya, K. Efrapeptin J, a new down-regulator of the molecular chaperone GRP78 from a marine Tolypocladium sp. J. Antibiot. (Tokyo),  2008, 61(6), 365-371.
[http://dx.doi.org/10.1038/ja.2008.51] [PMID: 18667784] 
[110] 
Oh, D.C.; Kauffman, C.A.; Jensen, P.R.; Fenical, W. Induced production of emericellamides A and B from the marine-derived fungus Emericella sp. in competing co-culture. J. Nat. Prod.,  2007, 70(4), 515-520.
[http://dx.doi.org/10.1021/np060381f] [PMID: 17323993] 
[111] 
Lee, Y.M.; Dang, H.T.; Li, J.; Zhang, P.; Hong, J.; Lee, C.O.; Jung, J.H. A Cytotoxic Fellutamide Analogue from the Sponge-Derived Fungus Aspergillus Versicolor. Bull. Korean Chem. Soc.,  2011, 32(10), 3817-3820.
[http://dx.doi.org/10.5012/bkcs.2011.32.10.3817] 
[112] 
Sun, P.; Maloney, K.N.; Nam, S-J.; Haste, N.M.; Raju, R.; Aalbersberg, W.; Jensen, P.R.; Nizet, V.; Hensler, M.E.; Fenical, W. Fijimycins A-C, three antibacterial etamycin-class depsipeptides from a marine-derived Streptomyces sp. Bioorg. Med. Chem.,  2011, 19(22), 6557-6562.
[http://dx.doi.org/10.1016/j.bmc.2011.06.053] [PMID: 21745747] 
[113] 
Kwan, J.C.; Ratnayake, R.; Abboud, K.A.; Paul, V.J.; Luesch, H. Grassypeptolides A-C, cytotoxic bis-thiazoline containing marine cyclodepsipeptides. J. Org. Chem.,  2010, 75(23), 8012-8023.
[http://dx.doi.org/10.1021/jo1013564] [PMID: 21047144] 
[114] 
Thornburg, C.C.; Thimmaiah, M.; Shaala, L.A.; Hau, A.M.; Malmo, J.M.; Ishmael, J.E.; Youssef, D.T.A.; McPhail, K.L. Cyclic depsipeptides, grassypeptolides D and E and Ibu-epidemethoxylyngbyastatin 3, from a Red Sea Leptolyngbya cyanobacterium. J. Nat. Prod.,  2011, 74(8), 1677-1685.
[http://dx.doi.org/10.1021/np200270d] [PMID: 21806012] 
[115] 
Popplewell, W.L.; Ratnayake, R.; Wilson, J.A.; Beutler, J.A.; Colburn, N.H.; Henrich, C.J.; McMahon, J.B.; McKee, T.C. Grassypeptolides F and G, cyanobacterial peptides from Lyngbya majuscula. J. Nat. Prod.,  2011, 74(8), 1686-1691.
[http://dx.doi.org/10.1021/np2005083] [PMID: 21806011] 
[116] 
Amagata, T.; Morinaka, B.I.; Amagata, A.; Tenney, K.; Valeriote, F.A.; Lobkovsky, E.; Clardy, J.; Crews, P. A chemical study of cyclic depsipeptides produced by a sponge-derived fungus. J. Nat. Prod.,  2006, 69(11), 1560-1565.
[http://dx.doi.org/10.1021/np060178k] [PMID: 17125221] 
[117] 
Tan, L.T.; Sitachitta, N.; Gerwick, W.H. The guineamides, novel cyclic depsipeptides from a Papua New Guinea collection of the marine cyanobacterium Lyngbya majuscula. J. Nat. Prod.,  2003, 66(6), 764-771.
[http://dx.doi.org/10.1021/np020492o] [PMID: 12828459] 
[118] 
Yang, L.; Tan, R.X.; Wang, Q.; Huang, W.Y.; Yin, Y.X. Antifungal Cyclopeptides from Halobacillus Litoralis YS3106 of Marine Origin. Tetrahedron Lett.,  2002, 43(37), 6545-6548.
[http://dx.doi.org/10.1016/S0040-4039(02)01458-2] 
[119] 
Tripathi, A.; Puddick, J.; Prinsep, M.R.; Lee, P.P.F.; Tan, L.T. Hantupeptin A, a cytotoxic cyclic depsipeptide from a Singapore collection of Lyngbya majuscula. J. Nat. Prod.,  2009, 72(1), 29-32.
[http://dx.doi.org/10.1021/np800448t] [PMID: 19093843] 
[120] 
Tripathi, A.; Puddick, J.; Prinsep, M.R.; Lee, P.P.F.; Tan, L.T. Hantupeptins B and C, cytotoxic cyclodepsipeptides from the marine cyanobacterium Lyngbya majuscula. Phytochemistry,  2010, 71(2-3), 307-311.https://doi.org/https://doi.org/10.1016/j.phytochem.2009.10.006
[http://dx.doi.org/10.1016/j.phytochem.2009.10.006] [PMID: 19913263] 
[121] 
Pereira, A.; Cao, Z.; Murray, T.F.; Gerwick, W.H. Hoiamide a, a sodium channel activator of unusual architecture from a consortium of two papua new Guinea cyanobacteria. Chem. Biol.,  2009, 16(8), 893-906.
[http://dx.doi.org/10.1016/j.chembiol.2009.06.012] [PMID: 19716479] 
[122] 
Davies-Coleman, M.T.; Dzeha, T.M.; Gray, C.A.; Hess, S.; Pannell, L.K.; Hendricks, D.T.; Arendse, C.E. Isolation of homodolastatin 16, a new cyclic depsipeptide from a Kenyan collection of Lyngbya majuscula. J. Nat. Prod.,  2003, 66(5), 712-715.
[http://dx.doi.org/10.1021/np030014t] [PMID: 12762816] 
[123] 
Cruz, L.J.; Insua, M.M.; Baz, J.P.; Trujillo, M.; Rodriguez-Mias, R.A.; Oliveira, E.; Giralt, E.; Albericio, F.; Cañedo, L.M. IB-01212, a new cytotoxic cyclodepsipeptide isolated from the marine fungus Clonostachys sp. ESNA-A009. J. Org. Chem.,  2006, 71(9), 3335-3338.
[http://dx.doi.org/10.1021/jo051600p] [PMID: 16626111] 
[124] 
Tareq, F.S.; Kim, J.H.; Lee, M.A.; Lee, H.S.; Lee, Y.J.; Lee, J.S.; Shin, H.J. Ieodoglucomides A and B from a marine-derived bacterium Bacillus licheniformis. Org. Lett.,  2012, 14(6), 1464-1467.
[http://dx.doi.org/10.1021/ol300202z] [PMID: 22360451] 
[125] 
Jiménez, J.I.; Vansach, T.; Yoshida, W.Y.; Sakamoto, B.; Pörzgen, P.; Horgen, F.D. Halogenated fatty acid amides and cyclic depsipeptides from an eastern Caribbean collection of the cyanobacterium Lyngbya majuscula. J. Nat. Prod.,  2009, 72(9), 1573-1578.
[http://dx.doi.org/10.1021/np900173d] [PMID: 19739598] 
[126] 
Williams, P.G.; Yoshida, W.Y.; Quon, M.K.; Moore, R.E.; Paul, V.J. Ulongapeptin, a cytotoxic cyclic depsipeptide from a Palauan marine cyanobacterium Lyngbya sp. J. Nat. Prod.,  2003, 66(5), 651-654.
[http://dx.doi.org/10.1021/np030050s] [PMID: 12762800] 
[127] 
Martín, J.; da S Sousa, T.; Crespo, G.; Palomo, S.; González, I.; Tormo, J.R.; de la Cruz, M.; Anderson, M.; Hill, R.T.; Vicente, F.; Genilloud, O.; Reyes, F. Kocurin, the true structure of PM181104, an anti-methicillin-resistant Staphylococcus aureus (MRSA) thiazolyl peptide from the marine-derived bacterium Kocuria palustris. Mar. Drugs,  2013, 11(2), 387-398.
[http://dx.doi.org/10.3390/md11020387] [PMID: 23380989] 
[128] 
Okamoto, S.; Iwasaki, A.; Ohno, O.; Suenaga, K. Isolation and Structure of Kurahyne B and Total Synthesis of the Kurahynes. J. Nat. Prod.,  2015, 78(11), 2719-2725.
[http://dx.doi.org/10.1021/acs.jnatprod.5b00662] [PMID: 26539973] 
[129] 
Tripathi, A.; Puddick, J.; Prinsep, M.R.; Rottmann, M.; Chan, K.P.; Chen, D.Y.K.; Tan, L.T. Lagunamide C, a cytotoxic cyclodepsipeptide from the marine cyanobacterium Lyngbya majuscula. Phytochemistry,  2011, 72(18), 2369-2375.
[http://dx.doi.org/10.1016/j.phytochem.2011.08.019] [PMID: 21903231] 
[130] 
Manam, R.R.; Teisan, S.; White, D.J.; Nicholson, B.; Grodberg, J.; Neuteboom, S.T.C.; Lam, K.S.; Mosca, D.A.; Lloyd, G.K.; Potts, B.C.M. Lajollamycin, a nitro-tetraene spiro-β-lactone-γ-lactam antibiotic from the marine actinomycete Streptomyces nodosus. J. Nat. Prod.,  2005, 68(2), 240-243.
[http://dx.doi.org/10.1021/np049725x] [PMID: 15730252] 
[131] 
Kalinovskaya, N.I.; Romanenko, L.A.; Kalinovsky, A.I.; Dmitrenok, P.S.; Dyshlovoy, S.A. A new antimicrobial and anticancer peptide producing by the marine deep sediment strain “Paenibacillus profundus” sp. nov. Sl 79. Nat. Prod. Commun.,  2013, 8(3), 381-384.
[http://dx.doi.org/10.1177/1934578X1300800326] [PMID: 23678816] 
[132] 
MacMillan, J.B.; Molinski, T.F. Lobocyclamide B from Lyngbya confervoides. Configuration and asymmetric synthesis of β-hydroxy-α-amino acids by (-)-sparteine-mediated aldol addition. Org. Lett.,  2002, 4(11), 1883-1886.
[http://dx.doi.org/10.1021/ol025876k] [PMID: 12027638] 
[133] 
Cho, J.Y.; Williams, P.G.; Kwon, H.C.; Jensen, P.R.; Fenical, W. Lucentamycins A-D, cytotoxic peptides from the marine-derived actinomycete Nocardiopsis lucentensis. J. Nat. Prod.,  2007, 70(8), 1321-1328.
[http://dx.doi.org/10.1021/np070101b] [PMID: 17630797] 
[134] 
Milligan, K.E.; Marquez, B.L.; Williamson, R.T.; Gerwick, W.H. Lyngbyabellin B, a toxic and antifungal secondary metabolite from the marine cyanobacterium Lyngbya majuscula. J. Nat. Prod.,  2000, 63(10), 1440-1443.
[http://dx.doi.org/10.1021/np000133y] [PMID: 11076574] 
[135] 
Matthew, S.; Salvador, L.A.; Schupp, P.J.; Paul, V.J.; Luesch, H. Cytotoxic halogenated macrolides and modified peptides from the apratoxin-producing marine cyanobacterium Lyngbya bouillonii from Guam. J. Nat. Prod.,  2010, 73(9), 1544-1552.
[http://dx.doi.org/10.1021/np1004032] [PMID: 20704304] 
[136] 
Choi, H.; Mevers, E.; Byrum, T.; Valeriote, F.A.; Gerwick, W.H. Lyngbyabellins K-N from Two Palmyra Atoll Collections of the Marine Cyanobacterium Moorea bouillonii. Eur. J. Org. Chem.,  2012, 2012(27), 5141-5150.
[http://dx.doi.org/10.1002/ejoc.201200691] [PMID: 24574859] 
[137] 
Luesch, H.; Yoshida, W.Y.; Moore, R.E.; Paul, V.J.; Mooberry, S.L. Isolation, structure determination, and biological activity of Lyngbyabellin A from the marine cyanobacterium lyngbya majuscula. J. Nat. Prod.,  2000, 63(5), 611-615.
[http://dx.doi.org/10.1021/np990543q] [PMID: 10843570] 
[138] 
Maru, N.; Ohno, O.; Uemura, D. Lyngbyacyclamides A and B, Novel Cytotoxic Peptides from Marine Cyanobacteria Lyngbya Sp. Tetrahedron Lett.,  2010, 51(49), 6384-6387.
[http://dx.doi.org/10.1016/j.tetlet.2010.06.105] 
[139] 
Williams, P.G.; Moore, R.E.; Paul, V.J. Isolation and structure determination of lyngbyastatin 3, a lyngbyastatin 1 homologue from the marine cyanobacterium Lyngbya majuscula. Determination of the configuration of the 4-amino-2,2-dimethyl-3-oxopentanoic acid unit in majusculamide C, dolastatin 12, lyngbyastatin 1, and lyngbyastatin 3 from cyanobacteria. J. Nat. Prod.,  2003, 66(10), 1356-1363.
[http://dx.doi.org/10.1021/np0302145] [PMID: 14575437] 
[140] 
Taori, K.; Matthew, S.; Rocca, J.R.; Paul, V.J.; Luesch, H. Lyngbyastatins 5-7, potent elastase inhibitors from Floridian marine cyanobacteria, Lyngbya spp. J. Nat. Prod.,  2007, 70(10), 1593-1600.
[http://dx.doi.org/10.1021/np0702436] [PMID: 17910513] 
[141] 
Horgen, F.D.; Kazmierski, E.B.; Westenburg, H.E.; Yoshida, W.Y.; Scheuer, P.J.; Malevamide, D. Malevamide D: isolation and structure determination of an isodolastatin H analogue from the marine cyanobacterium Symploca hydnoides. J. Nat. Prod.,  2002, 65(4), 487-491.
[http://dx.doi.org/10.1021/np010560r] [PMID: 11975485] 
[142] 
Gunasekera, S.P.; Owle, C.S.; Montaser, R.; Luesch, H.; Paul, V.J. Malyngamide 3 and cocosamides A and B from the marine cyanobacterium Lyngbya majuscula from Cocos Lagoon, Guam. J. Nat. Prod.,  2011, 74(4), 871-876.
[http://dx.doi.org/10.1021/np1008015] [PMID: 21341718] 
[143] 
Shaala, L.A.; Youssef, D.T.A.; McPhail, K.L.; Elbandy, M. Malyngamide 4, a New Lipopeptide from the Red Sea Marine Cyanobacterium Moorea Producens (Formerly Lyngbya Majuscula). Phytochem. Lett.,  2013, 6(2), 183-188.https://doi.org/https://doi.org/10.1016/j.phytol.2013.01.002
[http://dx.doi.org/10.1016/j.phytol.2013.01.002] 
[144] 
Zhou, X.; Huang, H.; Chen, Y.; Tan, J.; Song, Y.; Zou, J.; Tian, X.; Hua, Y.; Ju, J. Marthiapeptide A, an anti-infective and cytotoxic polythiazole cyclopeptide from a 60 L scale fermentation of the deep sea-derived Marinactinospora thermotolerans SCSIO 00652. J. Nat. Prod.,  2012, 75(12), 2251-2255.
[http://dx.doi.org/10.1021/np300554f] [PMID: 23215246] 
[145] 
Kanoh, K.; Matsuo, Y.; Adachi, K.; Imagawa, H.; Nishizawa, M.; Shizuri, Y. Mechercharmycins A and B, cytotoxic substances from marine-derived Thermoactinomyces sp. YM3-251. J. Antibiot. (Tokyo),  2005, 58(4), 289-292.
[http://dx.doi.org/10.1038/ja.2005.36] [PMID: 15981418] 
[146] 
Ishida, K.; Nakagawa, H.; Murakami, M. Microcyclamide, a cytotoxic cyclic hexapeptide from the cyanobacterium Microcystis aeruginosa. J. Nat. Prod.,  2000, 63(9), 1315-1317.
[http://dx.doi.org/10.1021/np000159p] [PMID: 11000050] 
[147] 
Gu, W.; Cueto, M.; Jensen, P.R.; Fenical, W.; Silverman, R.B. Microsporins A and B: New Histone Deacetylase Inhibitors from the Marine-Derived Fungus Microsporum Cf. Gypseum and the Solid-Phase Synthesis of Microsporin A. Tetrahedron,  2007, 63(28), 6535-6541.
[http://dx.doi.org/10.1016/j.tet.2007.04.025] 
[148] 
Andrianasolo, E.H.; Goeger, D.; Gerwick, W.H. Mitsoamide: A Cytotoxic Linear Lipopeptide from the Madagascar Marine Cyanobacterium Geitlerinema Sp. Pure Appl. Chem.,  2007, 79(4), 593-602.
[http://dx.doi.org/10.1351/pac200779040593] 
[149] 
Zhang, H.L.; Hua, H.M.; Pei, Y.H.; Yao, X.S. Three new cytotoxic cyclic acylpeptides from marine Bacillus sp. Chem. Pharm. Bull. (Tokyo),  2004, 52(8), 1029-1030.
[http://dx.doi.org/10.1248/cpb.52.1029] [PMID: 15305011] 
[150] 
Ma, Z.; Wang, N.; Hu, J.; Wang, S. Isolation and characterization of a new iturinic lipopeptide, mojavensin A produced by a marine-derived bacterium Bacillus mojavensis B0621A. J. Antibiot. (Tokyo),  2012, 65(6), 317-322.
[http://dx.doi.org/10.1038/ja.2012.19] [PMID: 22491138] 
[151] 
Cueto, M.; Jensen, P.R.; Fenical, W. N-Methylsansalvamide, a cytotoxic cyclic depsipeptide from a marine fungus of the genus fusarium. Phytochemistry,  2000, 55(3), 223-226.
[http://dx.doi.org/10.1016/S0031-9422(00)00280-6] [PMID: 11142846] 
[152] 
Kjaerulff, L.; Nielsen, A.; Mansson, M.; Gram, L.; Larsen, T.O.; Ingmer, H.; Gotfredsen, C.H. Identification of four new agr quorum sensing-interfering cyclodepsipeptides from a marine Photobacterium. Mar. Drugs,  2013, 11(12), 5051-5062.
[http://dx.doi.org/10.3390/md11125051] [PMID: 24351904] 
[153] 
Leet, J.E.; Li, W.; Ax, H.A.; Matson, J.A.; Huang, S.; Huang, R.; Cantone, J.L.; Drexler, D.; Dalterio, R.A.; Lam, K.S. Nocathiacins, new thiazolyl peptide antibiotics from Nocardia sp. II. Isolation, characterization, and structure determination. J. Antibiot. (Tokyo),  2003, 56(3), 232-242.
[http://dx.doi.org/10.7164/antibiotics.56.232] [PMID: 12760679] 
[154] 
Williams, P.G.; Yoshida, W.Y.; Moore, R.E.; Paul, V.J. Isolation and structure determination of obyanamide, a novel cytotoxic cyclic depsipeptide from the marine cyanobacterium Lyngbya confervoides. J. Nat. Prod.,  2002, 65(1), 29-31.
[http://dx.doi.org/10.1021/np0102253] [PMID: 11809060] 
[155] 
Um, S.; Choi, T.J.; Kim, H.; Kim, B.Y.; Kim, S-H.; Lee, S.K.; Oh, K-B.; Shin, J.; Oh, D-C. Ohmyungsamycins A and B: cytotoxic and antimicrobial cyclic peptides produced by Streptomyces sp. from a volcanic island. J. Org. Chem.,  2013, 78(24), 12321-12329.
[http://dx.doi.org/10.1021/jo401974g] [PMID: 24266328] 
[156] 
Williams, D.E.; Dalisay, D.S.; Patrick, B.O.; Matainaho, T.; Andrusiak, K.; Deshpande, R.; Myers, C.L.; Piotrowski, J.S.; Boone, C.; Yoshida, M.; Andersen, R.J. Padanamides A and B, highly modified linear tetrapeptides produced in culture by a Streptomyces sp. isolated from a marine sediment. Org. Lett.,  2011, 13(15), 3936-3939.
[http://dx.doi.org/10.1021/ol2014494] [PMID: 21749075] 
[157] 
Taniguchi, M.; Nunnery, J.K.; Engene, N.; Esquenazi, E.; Byrum, T.; Dorrestein, P.C.; Gerwick, W.H. Palmyramide A, a cyclic depsipeptide from a Palmyra Atoll collection of the marine cyanobacterium Lyngbya majuscula. J. Nat. Prod.,  2010, 73(3), 393-398.
[http://dx.doi.org/10.1021/np900428h] [PMID: 19839606] 
[158] 
Wyche, T.P.; Hou, Y.; Vazquez-Rivera, E.; Braun, D.; Bugni, T.S. Peptidolipins B-F, antibacterial lipopeptides from an ascidian-derived Nocardia sp. J. Nat. Prod.,  2012, 75(4), 735-740.
[http://dx.doi.org/10.1021/np300016r] [PMID: 22482367] 
[159] 
Miller, E.D.; Kauffman, C.A.; Jensen, P.R.; Fenical, W. Piperazimycins: cytotoxic hexadepsipeptides from a marine-derived bacterium of the genus Streptomyces. J. Org. Chem.,  2007, 72(2), 323-330.
[http://dx.doi.org/10.1021/jo061064g] [PMID: 17221946] 
[160] 
Luesch, H.; Pangilinan, R.; Yoshida, W.Y.; Moore, R.E.; Paul, V.J. Pitipeptolides A and B, new cyclodepsipeptides from the marine cyanobacterium Lyngbya majuscula. J. Nat. Prod.,  2001, 64(3), 304-307.
[http://dx.doi.org/10.1021/np000456u] [PMID: 11277744] 
[161] 
Meickle, T.; Gunasekera, S.P.; Liu, Y.; Luesch, H.; Paul, V.J. Porpoisamides A and B, two novel epimeric cyclic depsipeptides from a Florida Keys collection of Lyngbya sp. Bioorg. Med. Chem.,  2011, 19(22), 6576-6580.
[http://dx.doi.org/10.1016/j.bmc.2011.05.051] [PMID: 21705224] 
[162] 
Fiedler, H.P.; Bruntner, C.; Riedlinger, J.; Bull, A.T.; Knutsen, G.; Goodfellow, M.; Jones, A.; Maldonado, L.; Pathom-aree, W.; Beil, W.; Schneider, K.; Keller, S.; Sussmuth, R.D. Proximicin A, B and C, novel aminofuran antibiotic and anticancer compounds isolated from marine strains of the actinomycete Verrucosispora. J. Antibiot. (Tokyo),  2008, 61(3), 158-163.
[http://dx.doi.org/10.1038/ja.2008.125] [PMID: 18503194] 
[163] 
Ebrahim, W.; Kjer, J.; El Amrani, M.; Wray, V.; Lin, W.; Ebel, R.; Lai, D.; Proksch, P. Pullularins E and F, two new peptides from the endophytic fungus Bionectria ochroleuca isolated from the mangrove plant Sonneratia caseolaris. Mar. Drugs,  2012, 10(5), 1081-1091.
[http://dx.doi.org/10.3390/md10051081] [PMID: 22822358] 
[164] 
Tan, R.X.; Jensen, P.R.; Williams, P.G.; Fenical, W. Isolation and structure assignments of rostratins A-D, cytotoxic disulfides produced by the marine-derived fungus Exserohilum rostratum. J. Nat. Prod.,  2004, 67(8), 1374-1382.
[http://dx.doi.org/10.1021/np049920b] [PMID: 15332857] 
[165] 
Zheng, J.; Zhu, H.; Hong, K.; Wang, Y.; Liu, P.; Wang, X.; Peng, X.; Zhu, W. Novel cyclic hexapeptides from marine-derived fungus, Aspergillus sclerotiorum PT06-1. Org. Lett.,  2009, 11(22), 5262-5265.
[http://dx.doi.org/10.1021/ol902197z] [PMID: 19827766] 
[166] 
Zheng, J.; Xu, Z.; Wang, Y.; Hong, K.; Liu, P.; Zhu, W. Cyclic tripeptides from the halotolerant fungus Aspergillus sclerotiorum PT06-1. J. Nat. Prod.,  2010, 73(6), 1133-1137.
[http://dx.doi.org/10.1021/np100198h] [PMID: 20503985] 
[167] 
Yu, Z.; Lang, G.; Kajahn, I.; Schmaljohann, R.; Imhoff, J.F. Scopularides A and B, cyclodepsipeptides from a marine sponge-derived fungus, Scopulariopsis brevicaulis. J. Nat. Prod.,  2008, 71(6), 1052-1054.
[http://dx.doi.org/10.1021/np070580e] [PMID: 18412398] 
[168] 
Tan, L.T.; Cheng, X.C.; Jensen, P.R.; Fenical, W. Scytalidamides A and B, new cytotoxic cyclic heptapeptides from a marine fungus of the genus Scytalidium. J. Org. Chem.,  2003, 68(23), 8767-8773.
[http://dx.doi.org/10.1021/jo030191z] [PMID: 14604342] 
[169] 
Prompanya, C.; Fernandes, C.; Cravo, S.; Pinto, M.M.M.; Dethoup, T.; Silva, A.M.S.; Kijjoa, A. A new cyclic hexapeptide and a new isocoumarin derivative from the marine sponge-associated fungus Aspergillus similanensis KUFA 0013. Mar. Drugs,  2015, 13(3), 1432-1450.
[http://dx.doi.org/10.3390/md13031432] [PMID: 25789601] 
[170] 
Mansson, M.; Nielsen, A.; Kjærulff, L.; Gotfredsen, C.H.; Wietz, M.; Ingmer, H.; Gram, L.; Larsen, T.O. Inhibition of virulence gene expression in Staphylococcus aureus by novel depsipeptides from a marine photobacterium. Mar. Drugs,  2011, 9(12), 2537-2552.
[http://dx.doi.org/10.3390/md9122537] [PMID: 22363239] 
[171] 
Kralj, A.; Kehraus, S.; Krick, A.; van Echten-Deckert, G.; König, G.M. Two new depsipeptides from the marine fungus Spicellum roseum. Planta Med.,  2007, 73(4), 366-371.
[http://dx.doi.org/10.1055/s-2007-967131] [PMID: 17354168] 
[172] 
Molinski, T.F.; Reynolds, K.A.; Morinaka, B.I. Symplocin A, a linear peptide from the Bahamian cyanobacterium Symploca sp. Configurational analysis of N,N-dimethylamino acids by chiral-phase HPLC of naphthacyl esters. J. Nat. Prod.,  2012, 75(3), 425-431.
[http://dx.doi.org/10.1021/np200861n] [PMID: 22360587] 
[173] 
Taori, K.; Liu, Y.; Paul, V.J.; Luesch, H. Combinatorial strategies by marine cyanobacteria: symplostatin 4, an antimitotic natural dolastatin 10/15 hybrid that synergizes with the coproduced HDAC inhibitor largazole. ChemBioChem,  2009, 10(10), 1634-1639.
[http://dx.doi.org/10.1002/cbic.200900192] [PMID: 19514039] 
[174] 
Williams, P.G.; Yoshida, W.Y.; Moore, R.E.; Paul, V.J. Tasiamide, a cytotoxic peptide from the marine cyanobacterium Symploca sp. J. Nat. Prod.,  2002, 65(9), 1336-1339.
[http://dx.doi.org/10.1021/np020184q] [PMID: 12350160] 
[175] 
Williams, P.G.; Yoshida, W.Y.; Moore, R.E.; Paul, V.J. The isolation and structure elucidation of Tasiamide B, a 4-amino-3-hydroxy-5-phenylpentanoic acid containing peptide from the marine Cyanobacterium Symploca sp. J. Nat. Prod.,  2003, 66(7), 1006-1009.
[http://dx.doi.org/10.1021/np030114z] [PMID: 12880326] 
[176] 
Desjardine, K.; Pereira, A.; Wright, H.; Matainaho, T.; Kelly, M.; Andersen, R.J. Tauramamide, a lipopeptide antibiotic produced in culture by Brevibacillus laterosporus isolated from a marine habitat: structure elucidation and synthesis. J. Nat. Prod.,  2007, 70(12), 1850-1853.
[http://dx.doi.org/10.1021/np070209r] [PMID: 18044840] 
[177] 
Rungprom, W.; Siwu, E.R.O.; Lambert, L.K.; Dechsakulwatana, C.; Barden, M.C.; Kokpol, U.; Blanchfield, J.T.; Kita, M.; Garson, M.J. Cyclic Tetrapeptides from Marine Bacteria Associated with the Seaweed Diginea Sp. and the Sponge Halisarca Ectofibrosa. Tetrahedron,  2008, 64(14), 3147-3152.https://doi.org/https://doi.org/10.1016/j.tet.2008.01.089
[http://dx.doi.org/10.1016/j.tet.2008.01.089] 
[178] 
Engelhardt, K.; Degnes, K.F.; Kemmler, M.; Bredholt, H.; Fjaervik, E.; Klinkenberg, G.; Sletta, H.; Ellingsen, T.E.; Zotchev, S.B. Production of a new thiopeptide antibiotic, TP-1161, by a marine Nocardiopsis species. Appl. Environ. Microbiol.,  2010, 76(15), 4969-4976.
[http://dx.doi.org/10.1128/AEM.00741-10] [PMID: 20562278] 
[179] 
Sun, Y.; Tian, L.; Huang, Y.F.; Sha, Y.; Pei, Y.H. A new cyclotetrapeptide from marine fungus Trichoderma reesei. Pharmazie,  2006, 61(9), 809-810.
[http://dx.doi.org/10.1002/chin.200702178] [PMID: 17020165] 
[180] 
Pruksakorn, P.; Arai, M.; Kotoku, N.; Vilchèze, C.; Baughn, A.D.; Moodley, P.; Jacobs, W.R., Jr; Kobayashi, M. Trichoderins, novel aminolipopeptides from a marine sponge-derived Trichoderma sp., are active against dormant mycobacteria. Bioorg. Med. Chem. Lett.,  2010, 20(12), 3658-3663.https://doi.org/https://doi.org/10.1016/j.bmcl.2010.04.100
[http://dx.doi.org/10.1016/j.bmcl.2010.04.100] [PMID: 20483615] 
[181] 
Garo, E.; Starks, C.M.; Jensen, P.R.; Fenical, W.; Lobkovsky, E.; Clardy, J. Trichodermamides A and B, cytotoxic modified dipeptides from the marine-derived fungus Trichoderma virens. J. Nat. Prod.,  2003, 66(3), 423-426.
[http://dx.doi.org/10.1021/np0204390] [PMID: 12662106] 
[182] 
Bunyajetpong, S.; Yoshida, W.Y.; Sitachitta, N.; Kaya, K. Trungapeptins A-C, cyclodepsipeptides from the marine cyanobacterium Lyngbya majuscula. J. Nat. Prod.,  2006, 69(11), 1539-1542.
[http://dx.doi.org/10.1021/np050485a] [PMID: 17125217] 
[183] 
Li, D.; Carr, G.; Zhang, Y.; Williams, D.E.; Amlani, A.; Bottriell, H.; Mui, A.L.F.; Andersen, R.J. Turnagainolides A and B, cyclic depsipeptides produced in culture by a Bacillus sp.: isolation, structure elucidation, and synthesis. J. Nat. Prod.,  2011, 74(5), 1093-1099.
[http://dx.doi.org/10.1021/np200033y] [PMID: 21539394] 
[184] 
Luesch, H.; Williams, P.G.; Yoshida, W.Y.; Moore, R.E.; Paul, V.J. Ulongamides A-F, new β-amino acid-containing cyclodepsipeptides from Palauan collections of the marine cyanobacterium Lyngbya sp. J. Nat. Prod.,  2002, 65(7), 996-1000.
[http://dx.doi.org/10.1021/np0200461] [PMID: 12141859] 
[185] 
Liu, S.; Shen, Y. A New Cyclic Peptide from the Marine Fungal Strain Aspergillus Sp. AF119. Chem. Nat. Compd.,  2011, 47(5), 786-788.
[http://dx.doi.org/10.1007/s10600-011-0059-2] 
[186] 
Oku, N.; Kawabata, K.; Adachi, K.; Katsuta, A.; Shizuri, Y. Unnarmicins A and C, new antibacterial depsipeptides produced by marine bacterium Photobacterium sp. MBIC06485. J. Antibiot. (Tokyo),  2008, 61(1), 11-17.
[http://dx.doi.org/10.1038/ja.2008.103] [PMID: 18305354] 
[187] 
Matsuo, Y.; Kanoh, K.; Yamori, T.; Kasai, H.; Katsuta, A.; Adachi, K.; Shin-Ya, K.; Shizuri, Y. Urukthapelstatin A, a novel cytotoxic substance from marine-derived Mechercharimyces asporophorigenens YM11-542. I. Fermentation, isolation and biological activities. J. Antibiot. (Tokyo),  2007, 60(4), 251-255.
[http://dx.doi.org/10.1038/ja.2007.30] [PMID: 17456975] 
[188] 
Mevers, E.; Liu, W.T.; Engene, N.; Mohimani, H.; Byrum, T.; Pevzner, P.A.; Dorrestein, P.C.; Spadafora, C.; Gerwick, W.H. Cytotoxic veraguamides, alkynyl bromide-containing cyclic depsipeptides from the marine cyanobacterium cf. Oscillatoria margaritifera. J. Nat. Prod.,  2011, 74(5), 928-936.
[http://dx.doi.org/10.1021/np200077f] [PMID: 21488639] 
[189] 
Zhou, L-N.; Gao, H-Q.; Cai, S-X.; Zhu, T-J.; Gu, Q-Q.; Li, D-H. Two New Cyclic Pentapeptides from the Marine-Derived Fungus Aspergillus Versicolor. Helv. Chim. Acta,  2011, 94(6), 1065-1070.
[http://dx.doi.org/10.1002/hlca.201000408] 
[190] 
Boudreau, P.D.; Byrum, T.; Liu, W.T.; Dorrestein, P.C.; Gerwick, W.H. Viequeamide A, a cytotoxic member of the kulolide superfamily of cyclic depsipeptides from a marine button cyanobacterium. J. Nat. Prod.,  2012, 75(9), 1560-1570.
[http://dx.doi.org/10.1021/np300321b] [PMID: 22924493] 
[191] 
Han, B.; Gross, H.; McPhail, K.L.; Goeger, D.; Maier, C.S.; Gerwick, W.H.; Wewakamide, A.; Guineamide, G. Wewakamide A and guineamide G, cyclic depsipeptides from the marine cyanobacteria Lyngbya semiplena and Lyngbya majuscula. J. Microbiol. Biotechnol.,  2011, 21(9), 930-936.
[http://dx.doi.org/10.4014/jmb.1105.05011] [PMID: 21952369] 
[192] 
Sitachitta, N.; Williamson, R.T.; Gerwick, W.H. Yanucamides A and B, two new depsipeptides from an assemblage of the marine cyanobacteria Lyngbya majuscula and Schizothrix species. J. Nat. Prod.,  2000, 63(2), 197-200.
[http://dx.doi.org/10.1021/np990466z] [PMID: 10691708] 
[193] 
Suzumura, K.; Yokoi, T.; Funatsu, M.; Nagai, K.; Tanaka, K.; Zhang, H.; Suzuki, K. YM-266183 and YM-266184, novel thiopeptide antibiotics produced by Bacillus cereus isolated from a marine sponge II. Structure elucidation. J. Antibiot. (Tokyo),  2003, 56(2), 129-134.
[http://dx.doi.org/10.7164/antibiotics.56.129] [PMID: 12715872] 
[194] 
Oh, D-C.; Jensen, P.R.; Fenical, W. Zygosporamide, a Cytotoxic Cyclic Depsipeptide from the Marine-Derived Fungus Zygosporium Masonii. Tetrahedron Lett.,  2006, 47(48), 8625-8628.https://doi.org/https://doi.org/10.1016/j.tetlet.2006.08.113
[http://dx.doi.org/10.1016/j.tetlet.2006.08.113] 
[195] 
Alanjary, M.; Cano-Prieto, C.; Gross, H.; Medema, M. H. Computer-Aided Re-Engineering of Nonribosomal Peptide and Polyketide Biosynthetic Assembly Lines.  Natural Product Reports. Royal Society of Chemistry,  2019 1. September;, 1249-1261.
[http://dx.doi.org/10.1039/c9np00021f] 
[196] 
Yan, F.; Liu, G.; Chen, T.; Fu, X.; Niu, M-M. Structure-Based Virtual Screening and Biological Evaluation of Peptide Inhibitors for Polo-Box Domain. Molecules,  2019, 25(1), 107.
[http://dx.doi.org/10.3390/molecules25010107] [PMID: 31892137] 
[197] 
Ferrer, J-L.; Jez, J.M.; Bowman, M.E.; Dixon, R.A.; Noel, J.P. Structure of chalcone synthase and the molecular basis of plant polyketide biosynthesis. Nat. Struct. Biol.,  1999, 6(8), 775-784.
[http://dx.doi.org/10.1038/11553] [PMID: 10426957] 
[198] 
Abe, I.; Sano, Y.; Takahashi, Y.; Noguchi, H. Site-directed mutagenesis of benzalacetone synthase. The role of the Phe215 in plant type III polyketide synthases. J. Biol. Chem.,  2003, 278(27), 25218-25226.
[http://dx.doi.org/10.1074/jbc.M303276200] [PMID: 12724310] 
[199] 
Yu, D.; Xu, F.; Zeng, J.; Zhan, J. Type III polyketide synthases in natural product biosynthesis. IUBMB Life,  2012, 64(4), 285-295.
[http://dx.doi.org/10.1002/iub.1005] [PMID: 22362498] 
[200] 
Shimokawa, Y.; Morita, H.; Abe, I. Benzalacetone Synthase. In:  Frontiers in Plant Science; Frontiers Research Foundation, 2012. 21. March;
[http://dx.doi.org/10.3389/fpls.2012.00057] 
[201] 
Aiswarya, G.; Mallika, V.; Mur, L.A.J.; Soniya, E.V. Ectopic expression and functional characterization of type III polyketide synthase mutants from Emblica officinalis Gaertn. Plant Cell Rep.,  2016, 35(10), 2077-2090.
[http://dx.doi.org/10.1007/s00299-016-2020-0] [PMID: 27406087] 
[202] 
Baharum, H.; Morita, H.; Tomitsuka, A.; Lee, F-C.; Ng, K-Y.; Rahim, R.A.; Abe, I.; Ho, C-L. Molecular cloning, modeling, and site-directed mutagenesis of type III polyketide synthase from Sargassum binderi (Phaeophyta). Mar. Biotechnol. (NY),  2011, 13(5), 845-856.
[http://dx.doi.org/10.1007/s10126-010-9344-5] [PMID: 21181422] 
[203] 
Wanibuchi, K.; Morita, H.; Noguchi, H.; Abe, I. Enzymatic formation of an aromatic dodecaketide by engineered plant polyketide synthase. Bioorg. Med. Chem. Lett.,  2011, 21(7), 2083-2086.https://doi.org/https://doi.org/10.1016/j.bmcl.2011.01.135
[http://dx.doi.org/10.1016/j.bmcl.2011.01.135] [PMID: 21345674] 
[204] 
Vickery, C.R.; Cardenas, J.; Bowman, M.E.; Burkart, M.D.; Da Silva, N.A.; Noel, J.P. A coupled in vitro/in vivo approach for engineering a heterologous type III PKS to enhance polyketide biosynthesis in Saccharomyces cerevisiae. Biotechnol. Bioeng.,  2018, 115(6), 1394-1402.
[http://dx.doi.org/10.1002/bit.26564] [PMID: 29457628] 
[205] 
Austin, M.B.; Noel, J.P. The chalcone synthase superfamily of type III polyketide synthases. Nat. Prod. Rep.,  2003, 20(1), 79-110.
[http://dx.doi.org/10.1039/b100917f] [PMID: 12636085] 
[206] 
Li, C.; Zhang, R.; Wang, J.; Wilson, L.M.; Yan, Y. Protein Engineering for Improving and Diversifying Natural Product Biosynthesis. Trends Biotechnol.,  2020, 38(7), 729-744.
[http://dx.doi.org/10.1016/j.tibtech.2019.12.008] [PMID: 31954530] 
[207] 
Osuna, S.; Jiménez-Osés, G.; Noey, E.L.; Houk, K.N. Molecular dynamics explorations of active site structure in designed and evolved enzymes. Acc. Chem. Res.,  2015, 48(4), 1080-1089.
[http://dx.doi.org/10.1021/ar500452q] [PMID: 25738880] 
[208] 
Renata, H.; Wang, Z.J.; Arnold, F.H. Expanding the enzyme universe: accessing non-natural reactions by mechanism-guided directed evolution. Angew. Chem. Int. Ed. Engl.,  2015, 54(11), 3351-3367.
[http://dx.doi.org/10.1002/anie.201409470] [PMID: 25649694] 
[209] 
Zeymer, C.; Hilvert, D. Directed Evolution of Protein Catalysts. Annu. Rev. Biochem.,  2018, 87(1), 131-157.
[http://dx.doi.org/10.1146/annurev-biochem-062917-012034] [PMID: 29494241] 
[210] 
Arnold, F.H. Directed Evolution: Bringing New Chemistry to Life. Angew. Chem. Int. Ed. Engl.,  2018, 57(16), 4143-4148.
[http://dx.doi.org/10.1002/anie.201708408] [PMID: 29064156] 
[211] 
Rodriguez, A.; Strucko, T.; Stahlhut, S.G.; Kristensen, M.; Svenssen, D.K.; Forster, J.; Nielsen, J.; Borodina, I. Metabolic engineering of yeast for fermentative production of flavonoids. Bioresour. Technol.,  2017, 245(Pt B), 1645-1654.https://doi.org/https://doi.org/10.1016/j.biortech.2017.06.043
[http://dx.doi.org/10.1016/j.biortech.2017.06.043] [PMID: 28634125] 
[212] 
Palmer, C.M.; Miller, K.K.; Nguyen, A.; Alper, H.S. Engineering 4-coumaroyl-CoA derived polyketide production in Yarrowia lipolytica through a β-oxidation mediated strategy. Metab. Eng.,  2020, 57, 174-181.https://doi.org/https://doi.org/10.1016/j.ymben.2019.11.006
[http://dx.doi.org/10.1016/j.ymben.2019.11.006] [PMID: 31740389] 
[213] 
Karbalaei, M.; Rezaee, S.A.; Farsiani, H. Pichia pastoris: A highly successful expression system for optimal synthesis of heterologous proteins. J. Cell. Physiol.,  2020, 235(9), 5867-5881.
[http://dx.doi.org/10.1002/jcp.29583] [PMID: 32057111] 
[214] 
Gao, L.; Cai, M.; Shen, W.; Xiao, S.; Zhou, X.; Zhang, Y. Engineered fungal polyketide biosynthesis in Pichia pastoris: a potential excellent host for polyketide production. Microb. Cell Fact.,  2013, 12, 77.
[http://dx.doi.org/10.1186/1475-2859-12-77] [PMID: 24011431] 
[215] 
Xue, Y.; Kong, C.; Shen, W.; Bai, C.; Ren, Y.; Zhou, X.; Zhang, Y.; Cai, M. Methylotrophic yeast Pichia pastoris as a chassis organism for polyketide synthesis via the full citrinin biosynthetic pathway. J. Biotechnol.,  2017, 242, 64-72.https://doi.org/https://doi.org/10.1016/j.jbiotec.2016.11.031
[http://dx.doi.org/10.1016/j.jbiotec.2016.11.031] [PMID: 27913218] 
[216] 
Hadadi, N.; Hafner, J.; Shajkofci, A.; Zisaki, A.; Hatzimanikatis, V. ATLAS of Biochemistry: A Repository of All Possible Biochemical Reactions for Synthetic Biology and Metabolic Engineering Studies. ACS Synth. Biol.,  2016, 5(10), 1155-1166.
[http://dx.doi.org/10.1021/acssynbio.6b00054] [PMID: 27404214] 
[217] 
Riaz, M.R.; Preston, G.M.; Mithani, A. MAPPS: A Web-Based Tool for Metabolic Pathway Prediction and Network Analysis in the Postgenomic Era. ACS Synth. Biol.,  2020, 9(5), 1069-1082.
[http://dx.doi.org/10.1021/acssynbio.9b00397] [PMID: 32347714] 
[218] 
Caspi, R.; Billington, R.; Fulcher, C.A.; Keseler, I.M.; Kothari, A.; Krummenacker, M.; Latendresse, M.; Midford, P.E.; Ong, Q.; Ong, W.K.; Paley, S.; Subhraveti, P.; Karp, P.D. The MetaCyc database of metabolic pathways and enzymes. Nucleic Acids Res.,  2018, 46(D1), D633-D639.
[http://dx.doi.org/10.1093/nar/gkx935] [PMID: 29059334] 
[219] 
Wu, Z.; Kan, S. B. J.; Lewis, R. D.; Wittmann, B. J.; Arnold, F. H. Machine Learning-Assisted Directed Protein Evolution with Combinatorial Libraries.  Proc. Natl. Acad. Sci.,  2019, 116(18), 8852-8858.
[http://dx.doi.org/10.1073/pnas.1901979116] 
[220] 
Yang, K.K.; Wu, Z.; Arnold, F.H. Machine-learning-guided directed evolution for protein engineering. Nat. Methods,  2019, 16(8), 687-694.
[http://dx.doi.org/10.1038/s41592-019-0496-6] [PMID: 31308553] 
[221] 
Trollope, K.M.; Görgens, J.F.; Volschenk, H. Semirational Directed Evolution of Loop Regions in Aspergillus japonicus β-Fructofuranosidase for Improved Fructooligosaccharide Production. Appl. Environ. Microbiol.,  2015, 81(20), 7319-7329.
[http://dx.doi.org/10.1128/AEM.02134-15] [PMID: 26253664] 
[222] 
Li, H.; Gao, S.; Qiu, Y.; Liang, C.; Zhu, S.; Zheng, G. Genome mining integrating semi-rational protein engineering and nanoreactor design: roadmap for a robust biocatalyst for industrial resolution of Vince lactam. Appl. Microbiol. Biotechnol.,  2020, 104(3), 1109-1123.
[http://dx.doi.org/10.1007/s00253-019-10275-6] [PMID: 31828408] 
[223] 
Nielsen, J. Cell factory engineering for improved production of natural products. Nat. Prod. Rep.,  2019, 36(9), 1233-1236.
[http://dx.doi.org/10.1039/C9NP00005D] [PMID: 30997457] 
[224] 
Gassler, T.; Sauer, M.; Gasser, B.; Egermeier, M.; Troyer, C.; Causon, T.; Hann, S.; Mattanovich, D.; Steiger, M.G. The industrial yeast Pichia pastoris is converted from a heterotroph into an autotroph capable of growth on CO2. Nat. Biotechnol.,  2020, 38(2), 210-216.
[http://dx.doi.org/10.1038/s41587-019-0363-0] [PMID: 31844294] 
[225] 
Boddy, C.N. Bioinformatics tools for genome mining of polyketide and non-ribosomal peptides. J. Ind. Microbiol. Biotechnol.,  2014, 41(2), 443-450.
[http://dx.doi.org/10.1007/s10295-013-1368-1] [PMID: 24174214] 
[226] 
Bachmann, B.O.; Van Lanen, S.G.; Baltz, R.H. Microbial genome mining for accelerated natural products discovery: is a renaissance in the making? J. Ind. Microbiol. Biotechnol.,  2014, 41(2), 175-184.
[http://dx.doi.org/10.1007/s10295-013-1389-9] [PMID: 24342967] 
[227] 
Tremblay, N.; Hill, P.; Conway, K.R.; Boddy, C.N. The Use of Clustermine360 for the Analysis of Polyketide and Nonribosomal Peptide Biosynthetic Pathways. Methods in Molecular Biology; Humana Press Inc., 2016, Vol. 1401, pp. 233-252.
[228] 
Zotchev, S.B. Marine actinomycetes as an emerging resource for the drug development pipelines. J. Biotechnol.,  2012, 158(4), 168-175.https://doi.org/https://doi.org/10.1016/j.jbiotec.2011.06.002
[http://dx.doi.org/10.1016/j.jbiotec.2011.06.002] [PMID: 21683100] 
[229] 
Mahapatra, G.P.; Raman, S.; Nayak, S.; Gouda, S.; Das, G.; Patra, J.K. Metagenomics Approaches in Discovery and Development of New Bioactive Compounds from Marine Actinomycetes. Curr. Microbiol.,  2020, 77(4), 645-656.
[http://dx.doi.org/10.1007/s00284-019-01698-5] [PMID: 31069462] 
[230] 
Amos, G.C.A.; Borsetto, C.; Laskaris, P.; Krsek, M.; Berry, A.E.; Newsham, K.K.; Calvo-Bado, L.; Pearce, D.A.; Vallin, C.; Wellington, E.M.H. Designing and Implementing an Assay for the Detection of Rare and Divergent NRPS and PKS Clones in European, Antarctic and Cuban Soils. PLoS One,  2015, 10(9), e0138327.
[http://dx.doi.org/10.1371/journal.pone.0138327] [PMID: 26398766] 
[231] 
Kautsar, S.A.; Suarez Duran, H.G.; Blin, K.; Osbourn, A.; Medema, M.H. plantiSMASH: automated identification, annotation and expression analysis of plant biosynthetic gene clusters. Nucleic Acids Res.,  2017, 45(W1), W55-W63.
[http://dx.doi.org/10.1093/nar/gkx305] [PMID: 28453650] 
[232] 
O’Brien, R.V.; Davis, R.W.; Khosla, C.; Hillenmeyer, M.E. Computational identification and analysis of orphan assembly-line polyketide synthases. J. Antibiot. (Tokyo),  2014, 67(1), 89-97.
[http://dx.doi.org/10.1038/ja.2013.125] [PMID: 24301183] 
[233] 
Röttig, M.; Medema, M. H.; Blin, K.; Weber, T.; Rausch, C.; Kohlbacher, O. NRPSpredictor2--a Web Server for Predicting NRPS Adenylation Domain Specificity.  Nucleic Acids Res,  2011, 39(Web Server issue), W362-7.
[http://dx.doi.org/10.1093/nar/gkr323] 
[234] 
Kim, J.; Yi, G.S. PKMiner: a database for exploring type II polyketide synthases. BMC Microbiol.,  2012, 8(12), 169.
[http://dx.doi.org/10.1186/1471-2180-12-169] [PMID: 22871112] 
[235] 
Chevrette, M.G.; Aicheler, F.; Kohlbacher, O.; Currie, C.R.; Medema, M.H. SANDPUMA: ensemble predictions of nonribosomal peptide chemistry reveal biosynthetic diversity across Actinobacteria. Bioinformatics,  2017, 33(20), 3202-3210.
[http://dx.doi.org/10.1093/bioinformatics/btx400] [PMID: 28633438] 
[236] 
Zierep, P.F.; Padilla, N.; Yonchev, D.G.; Telukunta, K.K.; Klementz, D.; Günther, S. SeMPI: a genome-based secondary metabolite prediction and identification web server. Nucleic Acids Res.,  2017, 45(W1), W64-W71.
[http://dx.doi.org/10.1093/nar/gkx289] [PMID: 28453782] 
[237] 
Vijayan, M.; Chandrika, S.K.; Vasudevan, S.E. PKSIIIexplorer: TSVM approach for predicting Type III polyketide synthase proteins. Bioinformation,  2011, 6(3), 125-127.
[http://dx.doi.org/10.6026/97320630006125] [PMID: 21584189] 
[238] 
Helfrich, E.J.N.; Ueoka, R.; Dolev, A.; Rust, M.; Meoded, R.A.; Bhushan, A.; Califano, G.; Costa, R.; Gugger, M.; Steinbeck, C.; Moreno, P.; Piel, J. Automated structure prediction of trans-acyltransferase polyketide synthase products. Nat. Chem. Biol.,  2019, 15(8), 813-821.
[http://dx.doi.org/10.1038/s41589-019-0313-7] [PMID: 31308532] 
[239] 
Ziemert, N.; Podell, S.; Penn, K.; Badger, J.H.; Allen, E.; Jensen, P.R. The natural product domain seeker NaPDoS: a phylogeny based bioinformatic tool to classify secondary metabolite gene diversity. PLoS One,  2012, 7(3), e34064.
[http://dx.doi.org/10.1371/journal.pone.0034064] [PMID: 22479523] 
[240] 
Rai, A.; Saito, K.; Yamazaki, M. Integrated omics analysis of specialized metabolism in medicinal plants. Plant J.,  2017, 90(4), 764-787.
[http://dx.doi.org/10.1111/tpj.13485] [PMID: 28109168] 
[241] 
Wang, Q.; Liu, J.; Zhu, H. Genetic and Molecular Mechanisms Underlying Symbiotic Specificity in Legume-Rhizobium Interactions. Front. Plant Sci.,  2018, 9, 313.
[http://dx.doi.org/10.3389/fpls.2018.00313] [PMID: 29593768] 
[242] 
Chen, Y.; Yao, L.; Pan, W.; Guo, B.; Lin, S.; Wei, Y. An Integrated Analysis of Metabolomic and Transcriptomic Profiles Reveals Flavonoid Metabolic Differences between Anoectochilus Roxburghii and Anoectochilus Formosanus.  Process Biochem, 2020.https://doi.org/https://doi.org/10.1016/j.procbio.2020.07.004
[243] 
Agin, A.; Heintz, D.; Ruhland, E.; Chao de la Barca, J.M.; Zumsteg, J.; Moal, V.; Gauchez, A.S.; Namer, I. J. Metabolomics – an Overview. From Basic Principles to Potential Biomarkers (Part 1). Med. Nucl. (Paris),  2016, 40(1), 4-10.https://doi.org/https://doi.org/10.1016/j.mednuc.2015.12.006
[http://dx.doi.org/10.1016/j.mednuc.2015.12.006] 
[244] 
Bhandari, M.; Bhandari, A.; Bhandari, A. Sepbox technique in natural products. J. Young Pharm.,  2011, 3(3), 226-231.
[http://dx.doi.org/10.4103/0975-1483.83771] [PMID: 21897663] 
[245] 
Wang, T.; Li, Q.; Bi, K. Bioactive Flavonoids in Medicinal Plants: Structure, Activity and Biological Fate.  Asian J. Pharm. Sci.,  2018, 13(1), 12-23.https://doi.org/https://doi.org/10.1016/j.ajps.2017.08.004
[246] 
Fan, R.; Peng, C.; Zhang, X.; Qiu, D.; Mao, G.; Lu, Y.; Zeng, J. A comparative UPLC-Q-Orbitrap-MS untargeted metabolomics investigation of different parts of Clausena lansium (Lour.) Skeels.  Food science & nutrition.,  2020, 8(11), 5811-5822.
[http://dx.doi.org/10.1002/fsn3.1841] [PMID: 33282233] 
[247] 
Wong, F.T.; Khosla, C. Combinatorial biosynthesis of polyketides--a perspective. Curr. Opin. Chem. Biol.,  2012, 16(1-2), 117-123.
[http://dx.doi.org/10.1016/j.cbpa.2012.01.018] [PMID: 22342766] 
[248] 
Sun, H.; Liu, Z.; Zhao, H.; Ang, E. L. Recent Advances in Combinatorial Biosynthesis for Drug Discovery. Drug Design, Development and Therapy; Dove Medical Press Ltd., 2015, pp. 12. February;823-833.
[http://dx.doi.org/10.2147/DDDT.S63023] 
[249] 
Peirú, S.; Menzella, H.G.; Rodríguez, E.; Carney, J.; Gramajo, H. Production of the potent antibacterial polyketide erythromycin C in Escherichia coli. Appl. Environ. Microbiol.,  2005, 71(5), 2539-2547.
[http://dx.doi.org/10.1128/AEM.71.5.2539-2547.2005] [PMID: 15870344] 
[250] 
Hutchinson, C. R.; Fujii, D. Polyketide Synthase Gene Manipulation: A Structure-Function Approach in Engineering Novel Antibiotics. Annual Review of Microbiology; 201-238.Annual Reviews Inc., 1995, pp. 
[http://dx.doi.org/10.1146/annurev.mi.49.100195.001221] 
[251] 
Hojati, Z.; Milne, C.; Harvey, B.; Gordon, L.; Borg, M.; Flett, F.; Wilkinson, B.; Sidebottom, P.J.; Rudd, B.A.M.; Hayes, M.A.; Smith, C.P.; Micklefield, J. Structure, biosynthetic origin, and engineered biosynthesis of calcium-dependent antibiotics from Streptomyces coelicolor. Chem. Biol.,  2002, 9(11), 1175-1187.
[http://dx.doi.org/10.1016/S1074-5521(02)00252-1] [PMID: 12445768] 
[252] 
Luo, Y.; Li, B.Z.; Liu, D.; Zhang, L.; Chen, Y.; Jia, B.; Zeng, B.X.; Zhao, H.; Yuan, Y.J. Engineered biosynthesis of natural products in heterologous hosts. Chem. Soc. Rev.,  2015, 44(15), 5265-5290.
[http://dx.doi.org/10.1039/C5CS00025D] [PMID: 25960127] 
[253] 
Winn, M.; Fyans, J. K.; Zhuo, Y.; Micklefield, J. Recent Advances in Engineering Nonribosomal Peptide Assembly Lines. Natural Product Reports; Royal Society of Chemistry, 2016, pp. 1. February;317-347.
[http://dx.doi.org/10.1039/c5np00099h] 
[254] 
Yin, X.; Chen, Y.; Zhang, L.; Wang, Y.; Zabriskie, T.M. Enduracidin analogues with altered halogenation patterns produced by genetically engineered strains of Streptomyces fungicidicus. J. Nat. Prod.,  2010, 73(4), 583-589.
[http://dx.doi.org/10.1021/np900710q] [PMID: 20353165] 
[255] 
Kaniusaite, M.; Goode, R.J.A.; Tailhades, J.; Schittenhelm, R.B.; Cryle, M.J. Exploring Modular Reengineering Strategies to Redesign the Teicoplanin Non-Ribosomal Peptide Synthetase. Chem. Sci. (Camb.),  2020, 11(35), 9443-9458.
[http://dx.doi.org/10.1039/D0SC03483E] 
[256] 
Roberts, A.F.; Devos, Y.; Lemgo, G.N.Y.; Zhou, X. Biosafety research for non-target organism risk assessment of RNAi-based GE plants. Front. Plant Sci.,  2015, 6, 958.
[http://dx.doi.org/10.3389/fpls.2015.00958] [PMID: 26594220] 
[257] 
Jones-Rhoades, M.W.; Bartel, D.P.; Bartel, B. MicroRNAS and their regulatory roles in plants. Annu. Rev. Plant Biol.,  2006, 57(1), 19-53.
[http://dx.doi.org/10.1146/annurev.arplant.57.032905.105218] [PMID: 16669754] 
[258] 
Schwab, R.; Palatnik, J.F.; Riester, M.; Schommer, C.; Schmid, M.; Weigel, D. Specific effects of microRNAs on the plant transcriptome. Dev. Cell,  2005, 8(4), 517-527.https://doi.org/https://doi.org/10.1016/j.devcel.2005.01.018
[http://dx.doi.org/10.1016/j.devcel.2005.01.018] [PMID: 15809034] 
[259] 
Chen, X. MicroRNA biogenesis and function in plants. FEBS Lett.,  2005, 579(26), 5923-5931.
[http://dx.doi.org/10.1016/j.febslet.2005.07.071] [PMID: 16144699] 
[260] 
Saurabh, S.; Vidyarthi, A.S.; Prasad, D. RNA interference: concept to reality in crop improvement. Planta,  2014, 239(3), 543-564.
[http://dx.doi.org/10.1007/s00425-013-2019-5] [PMID: 24402564] 
[261] 
Allen, R.S.; Millgate, A.G.; Chitty, J.A.; Thisleton, J.; Miller, J.A.C.; Fist, A.J.; Gerlach, W.L.; Larkin, P.J. RNAi-mediated replacement of morphine with the nonnarcotic alkaloid reticuline in opium poppy. Nat. Biotechnol.,  2004, 22(12), 1559-1566.
[http://dx.doi.org/10.1038/nbt1033] [PMID: 15543134] 
[262] 
Qu, J.; Ye, J.; Fang, R. Artificial microRNA-mediated virus resistance in plants. J. Virol.,  2007, 81(12), 6690-6699.
[http://dx.doi.org/10.1128/JVI.02457-06] [PMID: 17344304] 
[263] 
Boudreau, R.L.; Monteys, A.M.; Davidson, B.L. Minimizing variables among hairpin-based RNAi vectors reveals the potency of shRNAs. RNA,  2008, 14(9), 1834-1844.
[http://dx.doi.org/10.1261/rna.1062908] [PMID: 18697922] 
[264] 
Khan, Z.; Ahmad, S.; Al-Ghimlas, F.; Al-Mutairi, S.; Joseph, L.; Chandy, R.; Sutton, D.A.; Guarro, J. Purpureocillium lilacinum as a cause of cavitary pulmonary disease: a new clinical presentation and observations on atypical morphologic characteristics of the isolate. J. Clin. Microbiol.,  2012, 50(5), 1800-1804.
[http://dx.doi.org/10.1128/JCM.00150-12] [PMID: 22322350] 
[265] 
Chakrabarti, M.; Meekins, K.M.; Gavilano, L.B.; Siminszky, B. Inactivation of the cytochrome P450 gene CYP82E2 by degenerative mutations was a key event in the evolution of the alkaloid profile of modern tobacco. New Phytol.,  2007, 175(3), 565-574.
[http://dx.doi.org/10.1111/j.1469-8137.2007.02116.x] [PMID: 17635231] 
[266] 
Gavilano, L.B.; Coleman, N.P.; Burnley, L-E.; Bowman, M.L.; Kalengamaliro, N.E.; Hayes, A.; Bush, L.; Siminszky, B. Genetic engineering of Nicotiana tabacum for reduced nornicotine content. J. Agric. Food Chem.,  2006, 54(24), 9071-9078.
[http://dx.doi.org/10.1021/jf0610458] [PMID: 17117792] 
[267] 
Xiong, A-S.; Yao, Q-H.; Peng, R-H.; Li, X.; Han, P-L.; Fan, H-Q. Different effects on ACC oxidase gene silencing triggered by RNA interference in transgenic tomato. Plant Cell Rep.,  2005, 23(9), 639-646.
[http://dx.doi.org/10.1007/s00299-004-0887-7] [PMID: 15503033] 
[268] 
Eady, C.C.; Kamoi, T.; Kato, M.; Porter, N.G.; Davis, S.; Shaw, M.; Kamoi, A.; Imai, S. Silencing onion lachrymatory factor synthase causes a significant change in the sulfur secondary metabolite profile. Plant Physiol.,  2008, 147(4), 2096-2106.
[http://dx.doi.org/10.1104/pp.108.123273] [PMID: 18583530] 
[269] 
Nishihara, M.; Nakatsuka, T.; Yamamura, S. Flavonoid components and flower color change in transgenic tobacco plants by suppression of chalcone isomerase gene. FEBS Lett.,  2005, 579(27), 6074-6078.
[http://dx.doi.org/10.1016/j.febslet.2005.09.073] [PMID: 16226261] 
[270] 
Llave, C.; Xie, Z.; Kasschau, K.D.; Carrington, J.C. Cleavage of Scarecrow-like mRNA targets directed by a class of Arabidopsis miRNA. Science,  2002, 297(5589), 2053-2056.
[http://dx.doi.org/10.1126/science.1076311] [PMID: 12242443] 
[271] 
Bartel, D.P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell,  2004, 116(2), 281-297.https://doi.org/https://doi.org/10.1016/S0092-8674(04)00045-5
[http://dx.doi.org/10.1016/S0092-8674(04)00045-5] [PMID: 14744438] 
[272] 
Saraiya, A.A.; Li, W.; Wang, C.C. Transition of a microRNA from repressing to activating translation depending on the extent of base pairing with the target. PLoS One,  2013, 8(2), e55672-e55672.
[http://dx.doi.org/10.1371/journal.pone.0055672] [PMID: 23405193] 
[273] 
Voinnet, O. Origin, biogenesis, and activity of plant microRNAs. Cell,  2009, 136(4), 669-687.https://doi.org/https://doi.org/10.1016/j.cell.2009.01.046
[http://dx.doi.org/10.1016/j.cell.2009.01.046] [PMID: 19239888] 
[274] 
Zhang, S.; Xie, M.; Ren, G.; Yu, B. CDC5, a DNA Binding Protein, Positively Regulates Posttranscriptional Processing and/or Transcription of Primary MicroRNA Transcripts.  Proc. Natl. Acad. Sci.,  2013, 110(43), 17588-17593.
[http://dx.doi.org/10.1073/pnas.1310644110] 
[275] 
Zhou, M.; Luo, H. MicroRNA-mediated gene regulation: potential applications for plant genetic engineering. Plant Mol. Biol.,  2013, 83(1-2), 59-75.
[http://dx.doi.org/10.1007/s11103-013-0089-1] [PMID: 23771582] 
[276] 
Eamens, A.; Wang, M.-B.; Smith, N. A.; Waterhouse, P. M. RNA Silencing in Plants: Yesterday, Today, and Tomorrow.  Plant Physiol.,  2008, 147(2), 456-468.
[http://dx.doi.org/10.1104/pp.108.117275] 
[277] 
Ossowski, S.; Schwab, R.; Weigel, D. Gene silencing in plants using artificial microRNAs and other small RNAs. Plant J.,  2008, 53(4), 674-690.
[http://dx.doi.org/10.1111/j.1365-313X.2007.03328.x] [PMID: 18269576] 
[278] 
Schwab, R.; Ossowski, S.; Riester, M.; Warthmann, N.; Weigel, D. Highly Specific Gene Silencing by Artificial MicroRNAs in Arabidopsis Plant Cell,  2006, 18(5), 1121-1133.
[279] 
Niu, Q-W.; Lin, S-S.; Reyes, J.L.; Chen, K-C.; Wu, H-W.; Yeh, S-D.; Chua, N-H. Expression of artificial microRNAs in transgenic Arabidopsis thaliana confers virus resistance. Nat. Biotechnol.,  2006, 24(11), 1420-1428.
[http://dx.doi.org/10.1038/nbt1255] [PMID: 17057702] 
[280] 
Sreekumar, S.; Soniya, E.V. Artificial MicroRNAs Promote High-Level Production of Biomolecules Through Metabolic Engineering of Phenylpropanoid Pathway. CRC. Crit. Rev. Plant Sci.,  2017, 36(5–6), 353-366.
[http://dx.doi.org/10.1080/07352689.2018.1444361] 
[281] 
Shi, R.; Yang, C.; Lu, S.; Sederoff, R.; Chiang, V.L. Specific down-regulation of PAL genes by artificial microRNAs in Populus trichocarpa. Planta,  2010, 232(6), 1281-1288.
[http://dx.doi.org/10.1007/s00425-010-1253-3] [PMID: 20725738] 
[282] 
Misra, P.; Pandey, A.; Tiwari, M.; Chandrashekar, K.; Sidhu, O.P.; Asif, M.H.; Chakrabarty, D.; Singh, P.K.; Trivedi, P.K.; Nath, P.; Tuli, R. Modulation of transcriptome and metabolome of tobacco by Arabidopsis transcription factor, AtMYB12, leads to insect resistance. Plant Physiol.,  2010, 152(4), 2258-2268.
[http://dx.doi.org/10.1104/pp.109.150979] [PMID: 20190095] 
[283] 
Joung, J.K.; Sander, J.D. TALENs: a widely applicable technology for targeted genome editing. Nat. Rev. Mol. Cell Biol.,  2013, 14(1), 49-55.
[http://dx.doi.org/10.1038/nrm3486] [PMID: 23169466] 
[284] 
Manghwar, H.; Li, B.; Ding, X.; Hussain, A.; Lindsey, K.; Zhang, X.; Jin, S. CRISPR/Cas Systems in Genome Editing: Methodologies and Tools for sgRNA Design, Off-Target Evaluation, and Strategies to Mitigate Off-Target Effects. Adv. Sci. (Weinh.),  2020, 7(6), 1902312.
[http://dx.doi.org/10.1002/advs.201902312] [PMID: 32195078] 
[285] 
Tao, W.; Yang, A.; Deng, Z.; Sun, Y. CRISPR/Cas9-Based Editing of Streptomyces for Discovery, Characterization, and Production of Natural Products. Front. Microbiol.,  2018, 9, 1660.
[http://dx.doi.org/10.3389/fmicb.2018.01660] [PMID: 30087666] 
[286] 
Westermann, L.; Neubauer, B.; Köttgen, M. Nobel Prize 2020 in Chemistry Honors CRISPR: A Tool for Rewriting the Code of Life 2020.
[http://dx.doi.org/10.1007/s00424-020-02497-9] 
[287] 
Kang, H-S.; Charlop-Powers, Z.; Brady, S.F. Multiplexed CRISPR/Cas9- and TAR-Mediated Promoter Engineering of Natural Product Biosynthetic Gene Clusters in Yeast. ACS Synth. Biol.,  2016, 5(9), 1002-1010.
[http://dx.doi.org/10.1021/acssynbio.6b00080] [PMID: 27197732] 
[288] 
Kim, H.; Ji, C-H.; Je, H-W.; Kim, J-P.; Kang, H-S. mpCRISTAR: Multiple Plasmid Approach for CRISPR/Cas9 and TAR-Mediated Multiplexed Refactoring of Natural Product Biosynthetic Gene Clusters. ACS Synth. Biol.,  2020, 9(1), 175-180.
[http://dx.doi.org/10.1021/acssynbio.9b00382] [PMID: 31800222] 
[289] 
Tong, Y.; Charusanti, P.; Zhang, L.; Weber, T.; Lee, S.Y. CRISPR-Cas9 Based Engineering of Actinomycetal Genomes. ACS Synth. Biol.,  2015, 4(9), 1020-1029.
[http://dx.doi.org/10.1021/acssynbio.5b00038] [PMID: 25806970] 
Rights & Permissions Print Cite
Article Metrics
36
1
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
For Visitors
DOI https://dx.doi.org/10.2174/1874467214666210319145816	Print ISSN 1874-4672
Publisher Name Bentham Science Publisher	Online ISSN 1874-4702
Current Molecular Pharmacology

Harnessing the Natural Pool of Polyketide and Non-ribosomal Peptide Family: A Route Map towards Novel Drug Development

Abstract

Graphical Abstract

Related Journals

Related Books

Related Articles
