A new Myxococcus xanthus gene cluster for the biosynthesis of the antibiotic saframycin Mx1 encoding a peptide synthetase.
نویسندگان
چکیده
The gene cluster for the biosynthesis of the heterocyclic quinone antibiotic saframycin Mx1 of Myxococcus xanthus DM504/15 was inactivated and tagged by Tn5 insertions. The tagged genes were cloned in Escherichia coli and used to select overlapping cosmid clones spanning 58 kb of the M. xanthus genome. Gene disruption experiments defined a > or = 18 kb contiguous DNA region involved in saframycin biosynthesis. Sequencing of part of this region revealed a large ORF containing two 600-amino-acid domains with similarity to peptide synthetase amino-acid-activating sequences, suggesting that saframycin Mx1 is synthesized by a nonribosomal multienzyme complex, similar to other bioactive peptides.
منابع مشابه
Saframycin Mx1, a new natural saframycin isolated from a myxobacterium.
A new natural saframycin was discovered in the culture broth of the myxobacterium, Myxococcus xanthus strain Mx x48. The fermentation and isolation of the antibiotic are described. The name, saframycin Mx1, is proposed. The compound appears to interact with cellular DNA.
متن کاملCharacterization of SafC, a catechol 4-O-methyltransferase involved in saframycin biosynthesis.
Members of the saframycin/safracin/ecteinascidin family of peptide natural products are potent antitumor agents currently under clinical development. Saframycin MX1, from Myxococcus xanthus, is synthesized by a nonribosomal peptide synthetase, SafAB, and an O-methyltransferase, SafC, although other proteins are likely involved in the pathway. SafC was overexpressed in Escherichia coli, purified...
متن کاملCharacterization of the saframycin A gene cluster from Streptomyces lavendulae NRRL 11002 revealing a nonribosomal peptide synthetase system for assembling the unusual tetrapeptidyl skeleton in an iterative manner.
Saframycin A (SFM-A), produced by Streptomyces lavendulae NRRL 11002, belongs to the tetrahydroisoquinoline family of antibiotics, and its core is structurally similar to the core of ecteinascidin 743, which is a highly potent antitumor drug isolated from a marine tunicate. In this study, the biosynthetic gene cluster for SFM-A was cloned and localized to a 62-kb contiguous DNA region. Sequence...
متن کاملGenetic analysis of polyketide synthase and peptide synthase genes of cyanobacteria as a mining tool for new pharmaceutical compounds
Cyanobacteria are considered a promising source for new pharmaceutical lead compounds and a large number of chemically diverse and bioactive metabolites have been obtained from cyanobacteria. Despite of several worldwide studies on prevalence of NRPSs and PKSs among the cyanobacteria, none of them included Iranian cyanobacteria of Kermanshah province. Therefore, the aim of this study was t...
متن کاملGenetic and functional analysis of genes required for the post-modification of the polyketide antibiotic TA of Myxococcus xanthus.
The antibiotic TA of Myxococcus xanthus is a complex macrocyclic polyketide, produced through successive condensations of acetate by a type I PKS (polyketide synthase) mechanism. The genes encoding TA biosynthesis are clustered on a 36 kb DNA fragment, which has been cloned and analysed. The chemical structure of TA and the mechanism by which it is synthesized indicate the need for several post...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Microbiology
دوره 141 ( Pt 8) شماره
صفحات -
تاریخ انتشار 1995