Unprecedented diversity of catalytic domains in the first four modules of the putative pederin polyketide synthase

Chembiochem. 2004 Jan 3;5(1):93-8. doi: 10.1002/cbic.200300782.

Abstract

Polyketides of the pederin group are highly potent antitumor compounds found in terrestrial beetles and marine sponges. Pederin is used by beetles of the genera Paederus and Paederidus as a chemical defense. We have recently identified a group of putative pederin biosynthesis genes and localized them to the genome of an as yet unculturable Pseudomonas sp. symbiont, the likely true pederin producer. However, this polyketide synthase cluster lacks several genes expected for pederin production. Here we report an additional polyketide synthase encoded on a separate region of the symbiont genome. It contains at least three novel catalytic domains that are predicted to be involved in pederin chain initiation and the formation of an unusual exomethylene bond. The region is bordered by mobility pseudogenes; this suggests that gene transposition led to the disjointed cluster organization. With this work, all putative pederin genes have been identified. Their heterologous expression in a culturable bacterium will provide important insights into how sustainable sources of invertebrate-derived drug candidates can be created.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Catalysis
  • Coleoptera / enzymology
  • Coleoptera / genetics*
  • Cosmids / genetics
  • DNA / biosynthesis
  • DNA / genetics
  • Gene Expression Regulation, Enzymologic / genetics
  • Gene Library
  • Molecular Sequence Data
  • Multienzyme Complexes / chemistry*
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism*
  • Pseudomonas aeruginosa / enzymology
  • Pseudomonas aeruginosa / metabolism
  • Pyrans / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Multienzyme Complexes
  • Pyrans
  • DNA
  • pederin