Stereoselective S-oxidation of flosequinan sulfide by rat hepatic flavin-containing monooxygenase 1A1 expressed in yeast

Biochem Pharmacol. 1994 Apr 20;47(8):1357-63. doi: 10.1016/0006-2952(94)90334-4.

Abstract

Rat hepatic flavin-containing monooxygenase (FMO) 1A1 expressed in yeast catalysed the S-oxidation of flosequinan sulfide (7-fluoro-1-methyl-3-methylthio-4-quinolone) to R(+)-flosequinan (sulfoxide form, R(+)-7-fluoro-1-methyl-3-methylsulfinyl-4-quinolone) but not to S(-)-flosequinan, and did not catalyse the oxidation of R(+)- and S(-)-flosequinan to flosequinan sulfone. The Km and Vmax for the stereoselective S-oxidation were 33 microM and 6.2 nmol per min per mg of microsomal protein, respectively. The S-oxidation was inhibited by 1-(1-naphthyl)-2-thiourea and thiobenzamide. n-Octylamine activated the S-oxidation with little change in stereoselectivity. The ability of the recombinant yeast to produce R(+)-flosequinan from flosequinan sulfide could be maintained for at least 2 days and exemplifies the value of a recombinant yeast expressing FMO as a stereoselective bioreactor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Enzyme Stability
  • Gene Expression
  • Microsomes, Liver / enzymology*
  • Oxidation-Reduction
  • Oxygenases / metabolism*
  • Quinolines / chemistry
  • Quinolines / metabolism*
  • Rats
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / enzymology*
  • Stereoisomerism

Substances

  • Quinolines
  • Recombinant Proteins
  • flosequinan
  • Oxygenases
  • dimethylaniline monooxygenase (N-oxide forming)