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Current Protein & Peptide Science

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ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

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Review Article

Application of Genetic Engineering Approaches to Improve Bacterial Metabolite Production

Author(s): Xin Xie, Jia-Wei Zhu, Yi Liu and Hui Jiang*

Volume 21, Issue 5, 2020

Page: [488 - 496] Pages: 9

DOI: 10.2174/1389203721666191223145827

Price: $65

Abstract

Genetic engineering is a powerful method to improve the fermentation yield of bacterial metabolites. Since many biosynthetic mechanisms of bacterial metabolites have been unveiled, genetic engineering approaches have been applied to various issues of biosynthetic pathways, such as transcription, translation, post-translational modification, enzymes, transporters, etc. In this article, natamycin, avermectins, gentamicins, piperidamycins, and β-valienamine have been chosen as examples to review recent progress in improving their production by genetic engineering approaches. In these cases, not only yields of target products have been increased, but also yields of by-products have been decreased, and new products have been created.

Keywords: Metabolite, genetic engineering, biosynthesis, enzyme, fermentation, metabolites.

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[1]
Zhao, G.; Yao, S.; Rothchild, K.W.; Liu, T.; Liu, Y.; Lian, J.; He, H.Y.; Ryan, K.S.; Du, Y.L. The biosynthetic gene cluster of the C-nucleoside antibiotic pyrazomycin with a rare pyrazole moiety. ChemBioChem, 2019.
[http://dx.doi.org/10.1002/cbic.201900449] [PMID: 31482654]
[2]
Martinet, L.; Naômé, A.; Deflandre, B.; Maciejewska, M.; Tellatin, D.; Tenconi, E.; Smargiasso, N.; de Pauw, E.; van Wezel, G.P.; Rigali, S. A single biosynthetic gene cluster is responsible for the production of bagremycin antibiotics and ferroverdin iron chelators. MBio, 2019, 10(4), e01230-e19.
[http://dx.doi.org/10.1128/mBio.01230-19] [PMID: 31409675]
[3]
Thomy, D.; Culp, E.; Adamek, M.; Cheng, E.Y.; Ziemert, N.; Wright, G.D.; Sass, P.; Brötz-Oesterhelt, H. The ADEP biosynthetic gene cluster in Streptomyces hawaiiensis NRRL 15010 reveals an accessory clpP gene as a novel antibiotic resistance factor. Appl. Environ. Microbiol., 2019, 85(20), e01292-e19.
[http://dx.doi.org/10.1128/AEM.01292-19] [PMID: 31399403]
[4]
Bosello, M.; Zeyadi, M.; Kraas, F.I.; Linne, U.; Xie, X.; Marahiel, M.A. Structural characterization of the heterobactin siderophores from Rhodococcus erythropolis PR4 and elucidation of their biosynthetic machinery. J. Nat. Prod., 2013, 76(12), 2282-2290.
[http://dx.doi.org/10.1021/np4006579] [PMID: 24274668]
[5]
Palazzotto, E.; Tong, Y.; Lee, S.Y.; Weber, T. Synthetic biology and metabolic engineering of actinomycetes for natural product discovery. Biotechnol. Adv., 2019, 37(6), 107366
[http://dx.doi.org/10.1016/j.biotechadv.2019.03.005] [PMID: 30853630]
[6]
Lee, N.; Hwang, S.; Lee, Y.; Cho, S.; Palsson, B.; Cho, B.K. Synthetic Biology Tools for Novel Secondary Metabolite Discovery in Streptomyces. J. Microbiol. Biotechnol., 2019, 29(5), 667-686.
[http://dx.doi.org/10.4014/jmb.1904.04015] [PMID: 31091862]
[7]
Aparicio, J.F.; Mendes, M.V.; Antón, N.; Recio, E.; Martín, J.F. Polyene macrolide antibiotic biosynthesis. Curr. Med. Chem., 2004, 11(12), 1645-1656.
[http://dx.doi.org/10.2174/0929867043365044] [PMID: 15180569]
[8]
el-Enshasy, H.A.; Farid, M.A.; el-Sayed, S.A. Influence of inoculum type and cultivation conditions on natamycin production by Streptomyces natalensis. J. Basic Microbiol., 2000, 40(5-6), 333-342.
[http://dx.doi.org/10.1002/1521-4028(200012)40:5/6<333:AID-JOBM333>3.0.CO;2-Q] [PMID: 11199493]
[9]
Chen, G.Q.; Lu, F.P.; Du, L.X. Natamycin production by Streptomyces gilvosporeus based on statistical optimization. J. Agric. Food Chem., 2008, 56(13), 5057-5061.
[http://dx.doi.org/10.1021/jf800479u] [PMID: 18537260]
[10]
Du, Y.L.; Chen, S.F.; Cheng, L.Y.; Shen, X.L.; Tian, Y.; Li, Y.Q. Identification of a novel Streptomyces chattanoogensis L10 and enhancing its natamycin production by overexpressing positive regulator ScnRII. J. Microbiol., 2009, 47(4), 506-513.
[http://dx.doi.org/10.1007/s12275-009-0014-0] [PMID: 19763427]
[11]
Liu, S.P.; Yu, P.; Yuan, P.H.; Zhou, Z.X.; Bu, Q.T.; Mao, X.M.; Li, Y.Q. Sigma factor WhiGch positively regulates natamycin production in Streptomyces chattanoogensis L10. Appl. Microbiol. Biotechnol., 2015, 99(6), 2715-2726.
[http://dx.doi.org/10.1007/s00253-014-6307-1] [PMID: 25724582]
[12]
Yu, P.; Liu, S.P.; Bu, Q.T.; Zhou, Z.X.; Zhu, Z.H.; Huang, F.L.; Li, Y.Q. WblAch, a pivotal activator of natamycin biosynthesis and morphological differentiation in Streptomyces chattanoogensis L10, is positively regulated by AdpAch. Appl. Environ. Microbiol., 2014, 80(22), 6879-6887.
[http://dx.doi.org/10.1128/AEM.01849-14] [PMID: 25172865]
[13]
Yu, P.; Bu, Q.T.; Tang, Y.L.; Mao, X.M.; Li, Y.Q. Bidirectional Regulation of AdpAch in Controlling the Expression of scnRI and scnRII in the Natamycin Biosynthesis of Streptomyces chattanoogensis L10. Front. Microbiol., 2018, 9, 316.
[http://dx.doi.org/10.3389/fmicb.2018.00316] [PMID: 29551998]
[14]
Du, Y.L.; Li, S.Z.; Zhou, Z.; Chen, S.F.; Fan, W.M.; Li, Y.Q. The pleitropic regulator AdpAch is required for natamycin biosynthesis and morphological differentiation in Streptomyces chattanoogensis. Microbiology, 2011, 157(Pt 5), 1300-1311.
[http://dx.doi.org/10.1099/mic.0.046607-0] [PMID: 21330439]
[15]
Antón, N.; Mendes, M.V.; Martín, J.F.; Aparicio, J.F. Identification of PimR as a positive regulator of pimaricin biosynthesis in Streptomyces natalensis. J. Bacteriol., 2004, 186(9), 2567-2575.
[http://dx.doi.org/10.1128/JB.186.9.2567-2575.2004] [PMID: 15090496]
[16]
Antón, N.; Santos-Aberturas, J.; Mendes, M.V.; Guerra, S.M.; Martín, J.F.; Aparicio, J.F. PimM, a PAS domain positive regulator of pimaricin biosynthesis in Streptomyces natalensis. Microbiology, 2007, 153(Pt 9), 3174-3183.
[http://dx.doi.org/10.1099/mic.0.2007/009126-0] [PMID: 17768260]
[17]
Recio, E.; Colinas, A.; Rumbero, A.; Aparicio, J.F.; Martín, J.F. PI factor, a novel type quorum-sensing inducer elicits pimaricin production in Streptomyces natalensis. J. Biol. Chem., 2004, 279(40), 41586-41593.
[http://dx.doi.org/10.1074/jbc.M402340200] [PMID: 15231842]
[18]
Mendes, M.V.; Tunca, S.; Antón, N.; Recio, E.; Sola-Landa, A.; Aparicio, J.F.; Martín, J.F. The two-component phoR-phoP system of Streptomyces natalensis: Inactivation or deletion of phoP reduces the negative phosphate regulation of pimaricin biosynthesis. Metab. Eng., 2007, 9(2), 217-227.
[http://dx.doi.org/10.1016/j.ymben.2006.10.003] [PMID: 17142079]
[19]
Lee, K.M.; Lee, C.K.; Choi, S.U.; Park, H.R.; Kitani, S.; Nihira, T.; Hwang, Y.I. Cloning and in vivo functional analysis by disruption of a gene encoding the gamma-butyrolactone autoregulator receptor from Streptomyces natalensis. Arch. Microbiol., 2005, 184(4), 249-257.
[http://dx.doi.org/10.1007/s00203-005-0047-7] [PMID: 16228193]
[20]
Martín, J.F.; Aparicio, J.F. Enzymology of the polyenes pimaricin and candicidin biosynthesis. Methods Enzymol., 2009, 459, 215-242.
[http://dx.doi.org/10.1016/S0076-6879(09)04610-2] [PMID: 19362642]
[21]
Hosaka, T.; Ohnishi-Kameyama, M.; Muramatsu, H.; Murakami, K.; Tsurumi, Y.; Kodani, S.; Yoshida, M.; Fujie, A.; Ochi, K. Antibacterial discovery in actinomycetes strains with mutations in RNA polymerase or ribosomal protein S12. Nat. Biotechnol., 2009, 27(5), 462-464.
[http://dx.doi.org/10.1038/nbt.1538] [PMID: 19396160]
[22]
Hosaka, T.; Xu, J.; Ochi, K. Increased expression of ribosome recycling factor is responsible for the enhanced protein synthesis during the late growth phase in an antibiotic-overproducing Streptomyces coelicolor ribosomal rpsL mutant. Mol. Microbiol., 2006, 61(4), 883-897.
[http://dx.doi.org/10.1111/j.1365-2958.2006.05285.x] [PMID: 16859496]
[23]
Ochi, K.; Okamoto, S.; Tozawa, Y.; Inaoka, T.; Hosaka, T.; Xu, J.; Kurosawa, K. Ribosome engineering and secondary metabolite production. Adv. Appl. Microbiol., 2004, 56, 155-184.
[http://dx.doi.org/10.1016/S0065-2164(04)56005-7] [PMID: 15566979]
[24]
Beld, J.; Sonnenschein, E.C.; Vickery, C.R.; Noel, J.P.; Burkart, M.D. The phosphopantetheinyl transferases: catalysis of a post-translational modification crucial for life. Nat. Prod. Rep., 2014, 31(1), 61-108.
[http://dx.doi.org/10.1039/C3NP70054B] [PMID: 24292120]
[25]
Jiang, H.; Wang, Y.Y.; Ran, X.X.; Fan, W.M.; Jiang, X.H.; Guan, W.J.; Li, Y.Q. Improvement of natamycin production by engineering of phosphopantetheinyl transferases in Streptomyces chattanoogensis L10. Appl. Environ. Microbiol., 2013, 79(11), 3346-3354.
[http://dx.doi.org/10.1128/AEM.00099-13] [PMID: 23524668]
[26]
Bentley, S.D.; Chater, K.F.; Cerdeño-Tárraga, A.M.; Challis, G.L.; Thomson, N.R.; James, K.D.; Harris, D.E.; Quail, M.A.; Kieser, H.; Harper, D.; Bateman, A.; Brown, S.; Chandra, G.; Chen, C.W.; Collins, M.; Cronin, A.; Fraser, A.; Goble, A.; Hidalgo, J.; Hornsby, T.; Howarth, S.; Huang, C.H.; Kieser, T.; Larke, L.; Murphy, L.; Oliver, K.; O’Neil, S.; Rabbinowitsch, E.; Rajandream, M.A.; Rutherford, K.; Rutter, S.; Seeger, K.; Saunders, D.; Sharp, S.; Squares, R.; Squares, S.; Taylor, K.; Warren, T.; Wietzorrek, A.; Woodward, J.; Barrell, B.G.; Parkhill, J.; Hopwood, D.A. Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2). Nature, 2002, 417(6885), 141-147.
[http://dx.doi.org/10.1038/417141a] [PMID: 12000953]
[27]
Challis, G.L. Exploitation of the Streptomyces coelicolor A3(2) genome sequence for discovery of new natural products and biosynthetic pathways. J. Ind. Microbiol. Biotechnol., 2014, 41(2), 219-232.
[http://dx.doi.org/10.1007/s10295-013-1383-2] [PMID: 24322202]
[28]
Stanley, A.E.; Walton, L.J.; Kourdi Zerikly, M.; Corre, C.; Challis, G.L. Elucidation of the Streptomyces coelicolor pathway to 4-methoxy-2,2′-bipyrrole-5-carboxaldehyde, an intermediate in prodiginine biosynthesis. Chem. Commun. (Camb.), 2006, (38), 3981-3983.
[http://dx.doi.org/10.1039/B609556A] [PMID: 17003872]
[29]
Lu, Y.W.; San Roman, A.K.; Gehring, A.M. Role of phosphopantetheinyl transferase genes in antibiotic production by Streptomyces coelicolor. J. Bacteriol., 2008, 190(20), 6903-6908.
[http://dx.doi.org/10.1128/JB.00865-08] [PMID: 18689472]
[30]
Nguyen, K.T.; Ritz, D.; Gu, J.Q.; Alexander, D.; Chu, M.; Miao, V.; Brian, P.; Baltz, R.H. Combinatorial biosynthesis of novel antibiotics related to daptomycin. Proc. Natl. Acad. Sci. USA, 2006, 103(46), 17462-17467.
[http://dx.doi.org/10.1073/pnas.0608589103] [PMID: 17090667]
[31]
Wittmann, M.; Linne, U.; Pohlmann, V.; Marahiel, M.A. Role of DptE and DptF in the lipidation reaction of daptomycin. FEBS J., 2008, 275(21), 5343-5354.
[http://dx.doi.org/10.1111/j.1742-4658.2008.06664.x] [PMID: 18959760]
[32]
Robbel, L.; Marahiel, M.A. Daptomycin, a bacterial lipopeptide synthesized by a nonribosomal machinery. J. Biol. Chem., 2010, 285(36), 27501-27508.
[http://dx.doi.org/10.1074/jbc.R110.128181] [PMID: 20522545]
[33]
Wessels, P.; von Döhren, H.; Kleinkauf, H. Biosynthesis of acylpeptidolactones of the daptomycin type. A comparative analysis of peptide synthetases forming A21978C and A54145. Eur. J. Biochem., 1996, 242(3), 665-673.
[http://dx.doi.org/10.1111/j.1432-1033.1996.0665r.x] [PMID: 9022695]
[34]
Baltz, R.H. Genomics and the ancient origins of the daptomycin biosynthetic gene cluster. J. Antibiot. (Tokyo), 2010, 63(8), 506-511.
[http://dx.doi.org/10.1038/ja.2010.82] [PMID: 20648020]
[35]
Milne, C.; Powell, A.; Jim, J.; Al Nakeeb, M.; Smith, C.P.; Micklefield, J. Biosynthesis of the (2S,3R)-3-methyl glutamate residue of nonribosomal lipopeptides. J. Am. Chem. Soc., 2006, 128(34), 11250-11259.
[http://dx.doi.org/10.1021/ja062960c] [PMID: 16925444]
[36]
Nguyen, K.T.; Kau, D.; Gu, J.Q.; Brian, P.; Wrigley, S.K.; Baltz, R.H.; Miao, V. A glutamic acid 3-methyltransferase encoded by an accessory gene locus important for daptomycin biosynthesis in Streptomyces roseosporus. Mol. Microbiol., 2006, 61(5), 1294-1307.
[http://dx.doi.org/10.1111/j.1365-2958.2006.05305.x] [PMID: 16879412]
[37]
Liao, G.; Wang, L.; Liu, Q.; Guan, F.; Huang, Y.; Hu, C. Manipulation of kynurenine pathway for enhanced daptomycin production in Streptomyces roseosporus. Biotechnol. Prog., 2013, 29(4), 847-852.
[http://dx.doi.org/10.1002/btpr.1740] [PMID: 23666758]
[38]
Huang, D.; Wen, J.; Wang, G.; Yu, G.; Jia, X.; Chen, Y. In silico aided metabolic engineering of Streptomyces roseosporus for daptomycin yield improvement. Appl. Microbiol. Biotechnol., 2012, 94(3), 637-649.
[http://dx.doi.org/10.1007/s00253-011-3773-6] [PMID: 22406858]
[39]
Aparicio, J.F.; Fouces, R.; Mendes, M.V.; Olivera, N.; Martín, J.F. A complex multienzyme system encoded by five polyketide synthase genes is involved in the biosynthesis of the 26-membered polyene macrolide pimaricin in Streptomyces natalensis. Chem. Biol., 2000, 7(11), 895-905.
[http://dx.doi.org/10.1016/S1074-5521(00)00038-7] [PMID: 11094342]
[40]
Aparicio, J.F.; Colina, A.J.; Ceballos, E.; Martín, J.F. The biosynthetic gene cluster for the 26-membered ring polyene macrolide pimaricin. A new polyketide synthase organization encoded by two subclusters separated by functionalization genes. J. Biol. Chem., 1999, 274(15), 10133-10139.
[http://dx.doi.org/10.1074/jbc.274.15.10133] [PMID: 10187796]
[41]
Liu, S.P.; Yuan, P.H.; Wang, Y.Y.; Liu, X.F.; Zhou, Z.X.; Bu, Q.T.; Yu, P.; Jiang, H.; Li, Y.Q. Generation of the natamycin analogs by gene engineering of natamycin biosynthetic genes in Streptomyces chattanoogensis L10. Microbiol. Res., 2015, 173, 25-33.
[http://dx.doi.org/10.1016/j.micres.2015.01.013] [PMID: 25801968]
[42]
Mendes, M.V.; Recio, E.; Fouces, R.; Luiten, R.; Martín, J.F.; Aparicio, J.F. Engineered biosynthesis of novel polyenes: a pimaricin derivative produced by targeted gene disruption in Streptomyces natalensis. Chem. Biol., 2001, 8(7), 635-644.
[http://dx.doi.org/10.1016/S1074-5521(01)00033-3] [PMID: 11451665]
[43]
Mendes, M.V.; Antón, N.; Martín, J.F.; Aparicio, J.F. Characterization of the polyene macrolide P450 epoxidase from Streptomyces natalensis that converts de-epoxypimaricin into pimaricin. Biochem. J., 2005, 386(Pt 1), 57-62.
[http://dx.doi.org/10.1042/BJ20040490] [PMID: 15228385]
[44]
Caffrey, P.; Aparicio, J.F.; Malpartida, F.; Zotchev, S.B. Biosynthetic engineering of polyene macrolides towards generation of improved antifungal and antiparasitic agents. Curr. Top. Med. Chem., 2008, 8(8), 639-653.
[http://dx.doi.org/10.2174/156802608784221479] [PMID: 18473889]
[45]
Guo, J.; Huang, F.; Huang, C.; Duan, X.; Jian, X.; Leeper, F.; Deng, Z.; Leadlay, P.F.; Sun, Y. Specificity and promiscuity at the branch point in gentamicin biosynthesis. Chem. Biol., 2014, 21(5), 608-618.
[http://dx.doi.org/10.1016/j.chembiol.2014.03.005] [PMID: 24746560]
[46]
Park, S.R.; Park, J.W.; Ban, Y.H.; Sohng, J.K.; Yoon, Y.J. 2-Deoxystreptamine-containing aminoglycoside antibiotics: recent advances in the characterization and manipulation of their biosynthetic pathways. Nat. Prod. Rep., 2013, 30(1), 11-20.
[http://dx.doi.org/10.1039/C2NP20092A] [PMID: 23179168]
[47]
Cuccarese, M.F.; Singh, A.; Amiji, M.; O’Doherty, G.A. A novel use of gentamicin in the ROS-mediated sensitization of NCI-H460 lung cancer cells to various anticancer agents. ACS Chem. Biol., 2013, 8(12), 2771-2777.
[http://dx.doi.org/10.1021/cb4007024] [PMID: 24093441]
[48]
Kharel, M.K.; Basnet, D.B.; Lee, H.C.; Liou, K.; Moon, Y.H.; Kim, J.J.; Woo, J.S.; Sohng, J.K. Molecular cloning and characterization of a 2-deoxystreptamine biosynthetic gene cluster in gentamicin- producing Micromonospora echinospora ATCC15835. Mol. Cells, 2004, 18(1), 71-78.
[PMID: 15359126]
[49]
Unwin, J.; Standage, S.; Alexander, D.; Hosted, T., Jr; Horan, A.C.; Wellington, E.M. Gene cluster in Micromonospora echinospora ATCC15835 for the biosynthesis of the gentamicin C complex. J. Antibiot. (Tokyo), 2004, 57(7), 436-445.
[http://dx.doi.org/10.7164/antibiotics.57.436] [PMID: 15376556]
[50]
Bockenhauer, D.; Hug, M.J.; Kleta, R. Cystic fibrosis, aminoglycoside treatment and acute renal failure: the not so gentle micin. Pediatr. Nephrol., 2009, 24(5), 925-928.
[http://dx.doi.org/10.1007/s00467-008-1036-2] [PMID: 19005685]
[51]
Sandoval, R.M.; Reilly, J.P.; Running, W.; Campos, S.B.; Santos, J.R.; Phillips, C.L.; Molitoris, B.A. A non-nephrotoxic gentamicin congener that retains antimicrobial efficacy. J. Am. Soc. Nephrol., 2006, 17(10), 2697-2705.
[http://dx.doi.org/10.1681/ASN.2005101124] [PMID: 16971659]
[52]
Kobayashi, M.; Sone, M.; Umemura, M.; Nabeshima, T.; Nakashima, T.; Hellström, S. Comparisons of cochleotoxicity among three gentamicin compounds following intratympanic application. Acta Otolaryngol., 2008, 128(3), 245-249.
[http://dx.doi.org/10.1080/00016480701558948] [PMID: 18274912]
[53]
Huang, C.; Huang, F.; Moison, E.; Guo, J.; Jian, X.; Duan, X.; Deng, Z.; Leadlay, P.F.; Sun, Y. Delineating the biosynthesis of gentamicin x2, the common precursor of the gentamicin C antibiotic complex. Chem. Biol., 2015, 22(2), 251-261.
[http://dx.doi.org/10.1016/j.chembiol.2014.12.012] [PMID: 25641167]
[54]
Yoon, Y.J.; Kim, E.S.; Hwang, Y.S.; Choi, C.Y. Avermectin: biochemical and molecular basis of its biosynthesis and regulation. Appl. Microbiol. Biotechnol., 2004, 63(6), 626-634.
[http://dx.doi.org/10.1007/s00253-003-1491-4] [PMID: 14689246]
[55]
Li, M.; Chen, Z.; Zhang, X.; Song, Y.; Wen, Y.; Li, J. Enhancement of avermectin and ivermectin production by overexpression of the maltose ATP-binding cassette transporter in Streptomyces avermitilis. Bioresour. Technol., 2010, 101(23), 9228-9235.
[http://dx.doi.org/10.1016/j.biortech.2010.06.132] [PMID: 20655739]
[56]
Qiu, J.; Zhuo, Y.; Zhu, D.; Zhou, X.; Zhang, L.; Bai, L.; Deng, Z. Overexpression of the ABC transporter AvtAB increases avermectin production in Streptomyces avermitilis. Appl. Microbiol. Biotechnol., 2011, 92(2), 337-345.
[http://dx.doi.org/10.1007/s00253-011-3439-4] [PMID: 21713508]
[57]
Ullán, R.V.; Liu, G.; Casqueiro, J.; Gutiérrez, S.; Bañuelos, O.; Martín, J.F. The cefT gene of Acremonium chrysogenum C10 encodes a putative multidrug efflux pump protein that significantly increases cephalosporin C production. Mol. Genet. Genomics, 2002, 267(5), 673-683.
[http://dx.doi.org/10.1007/s00438-002-0702-5] [PMID: 12172807]
[58]
McDaniel, R.; Thamchaipenet, A.; Gustafsson, C.; Fu, H.; Betlach, M.; Ashley, G. Multiple genetic modifications of the erythromycin polyketide synthase to produce a library of novel “unnatural” natural products. Proc. Natl. Acad. Sci. USA, 1999, 96(5), 1846-1851.
[http://dx.doi.org/10.1073/pnas.96.5.1846] [PMID: 10051557]
[59]
Reeves, C.D.; Murli, S.; Ashley, G.W.; Piagentini, M.; Hutchinson, C.R.; McDaniel, R. Alteration of the substrate specificity of a modular polyketide synthase acyltransferase domain through site-specific mutations. Biochemistry, 2001, 40(51), 15464-15470.
[http://dx.doi.org/10.1021/bi015864r] [PMID: 11747421]
[60]
Yu, Y.; Bai, L.; Minagawa, K.; Jian, X.; Li, L.; Li, J.; Chen, S.; Cao, E.; Mahmud, T.; Floss, H.G.; Zhou, X.; Deng, Z. Gene cluster responsible for validamycin biosynthesis in Streptomyces hygroscopicus subsp. jinggangensis 5008. Appl. Environ. Microbiol., 2005, 71(9), 5066-5076.
[http://dx.doi.org/10.1128/AEM.71.9.5066-5076.2005] [PMID: 16151088]
[61]
Bai, L.; Li, L.; Xu, H.; Minagawa, K.; Yu, Y.; Zhang, Y.; Zhou, X.; Floss, H.G.; Mahmud, T.; Deng, Z. Functional analysis of the validamycin biosynthetic gene cluster and engineered production of validoxylamine A. Chem. Biol., 2006, 13(4), 387-397.
[http://dx.doi.org/10.1016/j.chembiol.2006.02.002] [PMID: 16632251]
[62]
Ogawa, S.; Kanto, M.; Suzuki, Y. Development and medical application of unsaturated carbaglycosylamine glycosidase inhibitors. Mini Rev. Med. Chem., 2007, 7(7), 679-691.
[http://dx.doi.org/10.2174/138955707781024508] [PMID: 17627580]
[63]
Suzuki, Y.; Ogawa, S.; Sakakibara, Y. Chaperone therapy for neuronopathic lysosomal diseases: competitive inhibitors as chemical chaperones for enhancement of mutant enzyme activities. Perspect. Medicin. Chem., 2009, 3, 7-19.
[http://dx.doi.org/10.4137/PMC.S2332] [PMID: 19812739]
[64]
Higaki, K.; Ninomiya, H.; Suzuki, Y.; Nanba, E. Candidate molecules for chemical chaperone therapy of GM1-gangliosidosis. Future Med. Chem., 2013, 5(13), 1551-1558.
[http://dx.doi.org/10.4155/fmc.13.123] [PMID: 24024947]
[65]
Cui, L.; Zhu, Y.; Guan, X.; Deng, Z.; Bai, L.; Feng, Y. De Novo Biosynthesis of β-Valienamine in Engineered Streptomyces hygroscopicus 5008. ACS Synth. Biol., 2016, 5(1), 15-20.
[http://dx.doi.org/10.1021/acssynbio.5b00138] [PMID: 26436873]

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