Biosynthesis of the myxobacterial antibiotic corallopyronin A

Chembiochem. 2010 Jun 14;11(9):1253-65. doi: 10.1002/cbic.201000085.

Abstract

Corallopyronin A is a myxobacterial compound with potent antibacterial activity. Feeding experiments with labelled precursors resulted in the deduction of all biosynthetic building blocks for corallopyronin A and revealed an unusual feature of this metabolite: its biosynthesis from two chains, one solely PKS-derived and the other NRPS/PKS-derived. The starter molecule is believed to be carbonic acid or its monomethyl ester. The putative corallopyronin A biosynthetic gene cluster is a trans-AT-type mixed PKS/NRPS gene cluster, containing a beta-branching cassette. Striking features of this gene cluster are a NRPS-like adenylation domain that is part of a PKS-type module and is believed to be responsible for glycine incorporation, as well as split modules with individual domains occurring on different genes. It is suggested that CorB is a trans-acting ketosynthase and it is proposed that it catalyses the Claisen condensation responsible for the interconnection of the two chains. Additionally, the stereochemistry of corallopyronin A was deduced by a combination of a modified Mosher's method and ozonolysis with subsequent chiral GC analyses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anti-Bacterial Agents / biosynthesis*
  • Anti-Bacterial Agents / chemistry
  • Lactones / chemistry
  • Lactones / metabolism*
  • Molecular Sequence Data
  • Multigene Family
  • Myxococcales / enzymology*
  • Peptide Synthases / genetics
  • Peptide Synthases / metabolism
  • Polyketide Synthases / genetics
  • Polyketide Synthases / metabolism
  • Sequence Alignment
  • Stereoisomerism

Substances

  • Anti-Bacterial Agents
  • Lactones
  • corallopyronin A
  • Polyketide Synthases
  • Peptide Synthases
  • non-ribosomal peptide synthase