Bioconversion of lovastatin to a novel statin by Amycolatopsis sp

Appl Microbiol Biotechnol. 2008 May;79(2):209-16. doi: 10.1007/s00253-008-1430-5.

Abstract

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase catalyzes the conversion of HMG-CoA to mevalonic acid, which plays a significant role in cholesterol synthesis. Several statins, inhibitors of HMG-CoA reductase, can be synthesized and converted by microorganisms. Among 700 strains obtained from culture collections, one strain could convert lovastatin to a novel statin, wuxistatin. The strain was identified as a member of the genus Amycolatopsis based on 16S rRNA gene sequence, morphology analysis, and chemotaxonomic properties. Wuxistatin, a novel HMG-CoA reductase inhibitor, was purified by chromatography, and the structure was determined by electrospray ionization mass and nuclear magnetic resonance spectroscopy. The results show that wuxistatin was butanoic acid, 2-methyl-,1,2,3,5,8,8a-hexahydro-5-hydroxy-7-methyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl) ethy]-1-naphthalenyl ester. An additional hydroxyl group was added to lovastatin at the 5-position to yield wuxistatin. This modification enhanced the intrinsic inhibitory activity (IC50) ofwuxistatin (41+/-5 nM) for fourfold compared with lovastatin (160+/-10 nM). A stoichiometric conversion of lovastatin to wuxistatin occurred.

MeSH terms

  • Actinomycetales / genetics
  • Actinomycetales / metabolism*
  • Butyrates / metabolism
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors*
  • Lovastatin / chemistry
  • Lovastatin / metabolism*
  • RNA, Ribosomal, 16S / analysis

Substances

  • Butyrates
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • RNA, Ribosomal, 16S
  • wuxistatin
  • Lovastatin