title: 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.
authors: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors: Jason M
authors: JM
authors: Crawford
authors: Cyril
authors: C
authors: Portmann
authors: Renee
authors: R
authors: Kontnik
authors: Christopher T
authors: CT
authors: Walsh
authors: Jon
authors: J
authors: Clardy
mesh_terms: D000595:Amino Acid Sequence; D047630:Depsipeptides / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010453:Peptide Synthases / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment; D013379:Substrate Specificity
chemical_list: D047630:Depsipeptides; C531271:xenematide; D010453:Peptide Synthases