Enantioselective alpha-hydroxylation of 2-arylacetic acid derivatives and buspirone catalyzed by engineered cytochrome P450 BM-3

J Am Chem Soc. 2006 May 10;128(18):6058-9. doi: 10.1021/ja061261x.

Abstract

Here we report that an engineered microbial cytochrome P450 BM-3 (CYP102A subfamily) efficiently catalyzes the alpha-hydroxylation of phenylacetic acid esters. This P450 BM-3 variant also produces the authentic human metabolite of buspirone, R-6-hydroxybuspirone, with 99.5% ee.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Buspirone / chemistry*
  • Catalysis
  • Cytochrome P-450 Enzyme System / chemistry*
  • Cytochrome P-450 Enzyme System / genetics
  • Hydroxylation
  • Mixed Function Oxygenases / chemistry*
  • Mixed Function Oxygenases / genetics
  • Mutagenesis, Site-Directed
  • NADPH-Ferrihemoprotein Reductase
  • Phenylacetates / chemistry*
  • Stereoisomerism

Substances

  • Bacterial Proteins
  • Phenylacetates
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • NADPH-Ferrihemoprotein Reductase
  • flavocytochrome P450 BM3 monoxygenases
  • Buspirone