Combinatorial biosynthesis of lipopeptide antibiotics in Streptomyces roseosporus

  title={Combinatorial biosynthesis of lipopeptide antibiotics in Streptomyces roseosporus},
  author={Richard H. Baltz and P. Dilkes Brian and Vivian P. W. Miao and Stephen K. Wrigley},
  journal={Journal of Industrial Microbiology and Biotechnology},
Daptomycin is a cyclic lipopeptide antibiotic produced by Streptomyces roseosporus. Cubicin® (daptomycin-for-injection) was approved in 2003 by the FDA to treat skin and skin structure infections caused by Gram-positive pathogens. Daptomycin is particularly significant in that it represents the first new natural product antibacterial structural class approved for clinical use in three decades. The daptomycin gene cluster contains three very large genes (dptA, dptBC, and dptD) that encode the… 

Combinatorial biosynthesis of novel antibiotics related to daptomycin

This study established a robust combinatorial biosynthesis platform to produce novel peptide antibiotics in sufficient quantities for antimicrobial screening and drug development.

Genetically Engineered Lipopeptide Antibiotics Related to A54145 and Daptomycin with Improved Properties

ABSTRACT Daptomycin is a cyclic lipopeptide antibiotic approved for the treatment of skin and skin structure infections caused by Gram-positive pathogens and for that of bacteremia and right-sided

Complementation of daptomycin dptA and dptD deletion mutations in trans and production of hybrid lipopeptide antibiotics.

Daptomycin is a lipopeptide antibiotic produced by Streptomyces roseosporus and recently commercialized as Cubicin (daptomycin-for-injection) for treatment of skin and skin-structure infections

Daptomycin: Mechanism of Action and Bacterial Resistance

It has been proposed that the bactericidal effect of daptomycin arises from the formation of oligomeric pores or channels, and experiments are reported that test and further characterize this proposed mode of action.

Mode of Action of Daptomycin, a Lipopeptide Antibiotic

The experiments contained in this thesis strongly suggest that the oligomer is the bactericidal form of daptomycin.

Daptomycin, a Bacterial Lipopeptide Synthesized by a Nonribosomal Machinery*

The structural properties of daptomycin, its biosynthesis, recent efforts for the generation of structural diversity, and its proposed mode of action are discussed.

NMR structural studies of the antibiotic lipopeptide daptomycin in DHPC micelles.

Daptomycin: a review of properties, clinical use, drug delivery and resistance.

This review examines the most recent literature evidences on daptomycin molecular structure, mechanism of action, bacterial spectrum, clinical uses, local delivery, toxicity and resistance.

Improvement of daptomycin yield by overexpression of the accessory genes of daptomycin gene cluster

The results above suggested that the upstream and downstream accessory genes of NRPS had positive cooperativity in the biosynthesis of daptomycin.



Heterologous production of daptomycin in Streptomyces lividans

Production in S. lividans was improved by deletion of genes encoding the production of actinorhodin and by medium optimization to control the chemical form of the calcium dependent antibiotic (CDA).

The lipopeptide antibiotic A54145 biosynthetic gene cluster from Streptomyces fradiae

A comparison of the structure and the biosynthetic gene cluster of A54145 with those of the related peptides showed many similarities, which may contribute to the design of experiments to address both fundamental and applied questions in lipopeptide biosynthesis, engineering and drug development.

Daptomycin biosynthesis in Streptomyces roseosporus: cloning and analysis of the gene cluster and revision of peptide stereochemistry.

The unexpected E-domain suggested that daptomycin would have d-Asn, rather than l- asn, as originally assigned, and this was confirmed by comparing stereospecific synthetic peptides and the natural product both chemically and microbiologically.

Synthesis and derivatization of daptomycin: a chemoenzymatic route to acidic lipopeptide antibiotics.

The recombinant cyclization domain of the Streptomyces coelicolor calcium-dependent antibiotic (CDA) nonribosomal peptide synthetase (NRPS) is shown to be a versatile tool for the chemoenzymatic generation of daptomycin derivatives.

A54145 a new lipopeptide antibiotic complex: microbiological evaluation.

A calcium dependence study on some of the factors showed that their in vitro antibacterial activity was greatly enhanced by the presence of calcium (50 mg/liter) in the media.

A54145, a new lipopeptide antibiotic complex: discovery, taxonomy, fermentation and HPLC.

Fermentation studies determined that superior antibiotic yields were obtained in stirred bioreactors in a soybean flour-molasses medium employing a continuous glucose feed, and the selection of hyper-productive mutants increased fermentation yields from less than 50 micrograms/ml to more than 1 mg/ml.

Lipopeptides, focusing on daptomycin, for the treatment of Gram-positive infections

  • B. Eisenstein
  • Biology, Medicine
    Expert opinion on investigational drugs
  • 2004
Cubicin™ (daptomycin for injection), the first member of a new class of antibacterials called cyclic lipopeptides, has a unique mechanism of action and exhibits a relatively prolonged concentration-dependent postantibiotic effect in vitro.

Enzymatic and chemical modifications of lipopeptide antibiotic A21978C: the synthesis and evaluation of daptomycin (LY146032).

The n-decanoyl analog of A21978C (LY146032) gave the best survival in the mouse acute toxicity test at a high dose of 1,000 mg/kg, iv and was chosen for further study.

Deacylation of A21978C, an acidic lipopeptide antibiotic complex, by Actinoplanes utahensis.

Eacylation was accomplished with semi-pure and tert-butoxycarbonyl (tert-BOC)-A21978C to yield the unaltered nucleus, which was then reacylated to form new analogs to inhibit Gram-positive bacteria.