A biosynthetic pathway to isovaleryl-CoA in myxobacteria: the involvement of the mevalonate pathway

Chembiochem. 2005 Feb;6(2):322-30. doi: 10.1002/cbic.200400261.

Abstract

A biosynthetic shunt pathway branching from the mevalonate pathway and providing starter units for branched-chain fatty acid and secondary metabolite biosynthesis has been identified in strains of the myxobacterium Stigmatella aurantiaca. This pathway is upregulated when the branched-chain alpha-keto acid dehydrogenase gene (bkd) is inactivated, thus impairing the normal branched-chain amino acid degradation process. We previously proposed that, in this pathway, isovaleryl-CoA is derived from 3,3-dimethylacrylyl-CoA (DMA-CoA). Here we show that DMA-CoA is an isomerization product of 3-methylbut-3-enoyl-CoA (3MB-CoA). This compound is directly derived from 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) by a decarboxylation/ dehydration reaction resembling the conversion of mevalonate 5-diphosphate to isopentenyl diphosphate. Incubation of cell-free extracts of a bkd mutant with HMG-CoA gave product(s) with the molecular mass of 3MB-CoA or DMA-CoA. The shunt pathway most likely also operates reversibly and provides an alternative source for the monomers of isoprenoid biosynthesis in myxobacteria that utilize L-leucine as precursor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl Coenzyme A / biosynthesis*
  • Acyl Coenzyme A / chemistry
  • Acyl Coenzyme A / metabolism
  • Animals
  • Glutarates / chemistry
  • Glutarates / metabolism
  • Leucine / metabolism
  • Methacrylates
  • Mevalonic Acid / chemistry
  • Mevalonic Acid / metabolism*
  • Molecular Structure
  • Myxococcales / chemistry
  • Myxococcales / metabolism*
  • Quinolines / chemistry
  • Quinolines / metabolism
  • Stigmatella aurantiaca / chemistry
  • Stigmatella aurantiaca / genetics
  • Stigmatella aurantiaca / metabolism
  • Thiazoles / chemistry
  • Thiazoles / metabolism

Substances

  • Acyl Coenzyme A
  • Glutarates
  • Methacrylates
  • Quinolines
  • Thiazoles
  • aurachin A
  • 3-hydroxy-3-methylglutaryl-coenzyme A
  • 3-methylglutaconic acid
  • isovaleryl-coenzyme A
  • myxothiazol
  • Leucine
  • Mevalonic Acid