Identification, characterization, and bioconversion of a new intermediate in valanimycin biosynthesis.

ABSTRACT: The antibiotic valanimycin is a naturally occurring azoxy compound isolated from Streptomyces viridifaciens. Detailed investigations have shown that valanimycin is derived from L-valine and L-serine via the intermediacy of O-(L-seryl)isobutylhydroxylamine. Sequence analysis of the valanimycin biosynthetic genes provides relatively few clues concerning the nature of the later stages of the pathway. Two exceptions are provided by the vlmJ and vlmK genes. The translation product of vlmJ exhibits similarity to diacylglycerol kinases, while the translation product of vlmK exhibits a weak similarity to the MmgE/PrpD superfamily of proteins. This superfamily includes 2-methylcitrate dehydratase. This communication describes the isolation and structure elucidation of valanimycin hydrate from vlmJ and vlmK mutants of S. viridifaciens. Additional studies have shown that the conversion of valanimycin hydrate into valanimycin by S. viridifaciens requires both the vlmJ and vlmK genes and that VlmJ catalyzes the ATP-dependent phosphorylation of the hydroxyl group of valanimycin hydrate prior to VlmK-catalyzed dehydration.

SUBMITTER: Garg RP 

PROVIDER: S-EPMC2726733 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature