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Org Lett. 2011 Oct 7;13(19):5144-7. doi: 10.1021/ol2020237. Epub 2011 Sep 2.

NRPS substrate promiscuity diversifies the xenematides.

Author information

1
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.

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.

PMID:
21888371
PMCID:
PMC3184645
DOI:
10.1021/ol2020237
[Indexed for MEDLINE]
Free PMC Article

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