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NRPS substrate promiscuity diversifies the xenematides.


ABSTRACT: Xenematide, a cyclic depsipeptide antibiotic produced by Xenorhabdus nematophila, had a candidate nonribosomal peptide synthetase (NRPS) with atypical features. Differential metabolite analysis between a mutant and wildtype validated that this stand-alone NRPS was required for xenematide production, and further analysis led to a series of new xenematide derivatives encoded by the same NRPS. Our results indicate that adenylation domain promiscuity and relaxed downstream processing in the X. nematophila NRPS provide a conduit for xenematide diversification.

SUBMITTER: Crawford JM 

PROVIDER: S-EPMC3184645 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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NRPS substrate promiscuity diversifies the xenematides.

Crawford Jason M JM   Portmann Cyril C   Kontnik Renee R   Walsh Christopher T CT   Clardy Jon J  

Organic letters 20110902 19


Xenematide, a cyclic depsipeptide antibiotic produced by Xenorhabdus nematophila, had a candidate nonribosomal peptide synthetase (NRPS) with atypical features. Differential metabolite analysis between a mutant and wildtype validated that this stand-alone NRPS was required for xenematide production, and further analysis led to a series of new xenematide derivatives encoded by the same NRPS. Our results indicate that adenylation domain promiscuity and relaxed downstream processing in the X. nemat  ...[more]

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