Abstract
Daptomycin is a clinically important antibiotic approved for the treatment of complicated skin and skin structure infections caused by Gram-positive pathogens, and for the treatment of bacteremia and endocarditis caused by Staphylococcus aureus. Daptomycin and related acidic cyclic lipopeptide antibiotics have ten amino acids in the ring, and exocyclic tails containing one or three amino acids. The N-termini of the exocyclic amino acids are generally coupled to long chain fatty acids. Biosynthesis is initiated by the coupling of fatty acids to the N-terminal amino acids, followed by the coupling of the remaining amino acids by nonribosomal peptide synthetase (NRPS) mechanisms, then cyclization and release of the lipopeptides. The biosynthetic genes for daptomycin, calcium dependent antibiotic (CDA), A54145 and friulimicin have been cloned, sequenced, analyzed bioinformatically, and in some cases genetically or biochemically. The information on the organization and expression of the NRPS and other genes has been exploited to generate combinatorial libraries of hybrid lipopeptide antibiotics related to daptomycin, including several compounds with very good antibacterial activities.
Keywords: nonribosomal peptide synthetase, Streptomyes lividans, acyl carrier protein, dptG gene, A54145, amphomycins, friulimicins
Current Topics in Medicinal Chemistry
Title: Biosynthesis and Genetic Engineering of Lipopeptide Antibiotics Related to Daptomycin
Volume: 8 Issue: 8
Author(s): Richard H. Baltz
Affiliation:
Keywords: nonribosomal peptide synthetase, Streptomyes lividans, acyl carrier protein, dptG gene, A54145, amphomycins, friulimicins
Abstract: Daptomycin is a clinically important antibiotic approved for the treatment of complicated skin and skin structure infections caused by Gram-positive pathogens, and for the treatment of bacteremia and endocarditis caused by Staphylococcus aureus. Daptomycin and related acidic cyclic lipopeptide antibiotics have ten amino acids in the ring, and exocyclic tails containing one or three amino acids. The N-termini of the exocyclic amino acids are generally coupled to long chain fatty acids. Biosynthesis is initiated by the coupling of fatty acids to the N-terminal amino acids, followed by the coupling of the remaining amino acids by nonribosomal peptide synthetase (NRPS) mechanisms, then cyclization and release of the lipopeptides. The biosynthetic genes for daptomycin, calcium dependent antibiotic (CDA), A54145 and friulimicin have been cloned, sequenced, analyzed bioinformatically, and in some cases genetically or biochemically. The information on the organization and expression of the NRPS and other genes has been exploited to generate combinatorial libraries of hybrid lipopeptide antibiotics related to daptomycin, including several compounds with very good antibacterial activities.
Export Options
About this article
Cite this article as:
Baltz H. Richard, Biosynthesis and Genetic Engineering of Lipopeptide Antibiotics Related to Daptomycin, Current Topics in Medicinal Chemistry 2008; 8 (8) . https://dx.doi.org/10.2174/156802608784221497
DOI https://dx.doi.org/10.2174/156802608784221497 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Adaptogens—History and Future Perspectives
Adaptogens are pharmacologically active compounds or plant extracts that are associated with the ability to enhance the body’s stability against stress. The intake of adaptogens is associated not only with a better ability to adapt to stress and maintain or normalise metabolic functions but also with better mental and physical ...read more
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Virtual Screening for the Development of New Effective Compounds Against Staphylococcus aureus
Current Medicinal Chemistry Chemical Countermeasures for the Control of Bacterial Biofilms: Effective Compounds and Promising Targets
Current Medicinal Chemistry Optimal antibiotic dosage for chronic kidney disease patient: a pharmacological manual for oral clinicians
Recent Patents on Anti-Infective Drug Discovery First Report on the Characteristics of Methicillin-Resistant <i>Staphylococcus Capitis</i> Isolates and an NRCS-A-clone Related Isolate Obtained from Iranian Children
Infectious Disorders - Drug Targets Neuroprotective Effects of Ginkgolide B Against Ischemic Stroke: A Review of Current Literature
Current Topics in Medicinal Chemistry Systemic Fungal Infections Caused by Candida Species: Epidemiology, Infection Process and Virulence Attributes
Current Drug Targets Novel Strategies for Combating Pathogenic Biofilms Using Plant Products and Microbial Antibiosis
Current Pharmaceutical Biotechnology Long-term Outcomes of Mitral Valve Repair Versus Replacement for Degenerative Disease: A Systematic Review
Current Cardiology Reviews Effect of Treatment with Caspofungin on the Diagnosis of Fungal Infections by Gamma Scintigraphy
Current Radiopharmaceuticals Oral Factor Xa (FXa) Inhibitors for Treatment of Heparin-induced Thrombocytopenia (HIT)
Current Drug Therapy Isolation of <i>Morganella Morganii</i> and <i>Providencia</i> Species from Clinical Samples in a Tertiary Care Hospital in North India
Infectious Disorders - Drug Targets Halitosis Vaccines Targeting FomA, a Biofilm-bridging Protein of Fusobacteria nucleatum
Current Molecular Medicine Q Fever Endocarditis
Infectious Disorders - Drug Targets Pediatric Heart Failure in the Developing World
Reviews on Recent Clinical Trials Antibiotic Prophylaxis in Urologic Prosthetic Surgery
Current Pharmaceutical Design The Bovine Basic Pancreatic Trypsin Inhibitor (Kunitz Inhibitor): A Milestone Protein
Current Protein & Peptide Science Susceptibility of Intracellular Coxiella burnetii to Antimicrobial Peptides in Mouse Fibroblast Cells
Protein & Peptide Letters The Management of the Infected Diabetic Foot
Current Diabetes Reviews Bacterial Infection Probes and Imaging Strategies in Clinical Nuclear Medicine and Preclinical Molecular Imaging
Current Topics in Medicinal Chemistry Structure-Function Relationships in Anti-DNA and Anti-Phospholipid Antibodies and their Relevance to the Pathogenesis of Disease
Current Rheumatology Reviews