S-oxidation of (+)-cis-3,5-dimethyl-2-(3-pyridyl)-thiazolidin-4-one hydrochloride by rat hepatic flavin-containing monooxygenase 1 expressed in yeast

Abstract

1. Rat hepatic flavin-containing monooxygenase 1 (FMO1) expressed in yeast catalyzed the S-oxidation of (+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride (SM-12502) in vitro.

2. S-oxidation was inhibited by 1-(1-naphthyl)-2-thiourea and thiobenzamide, known inhibitors of FMO, but was not enhanced by n-octylamine, a known enhancer of FMO.

3. The rate of S-oxide formation from SM-12502 was about four-fold lower than that from (β)-trans-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride (SM-9979) and enantioselectivity and diastereoselectivity of the S-oxidation reaction were observed.

4. The ability of the recombinant yeast to produce the S-oxide from SM-12502 was maintained for long periods and exemplifies the recombinant yeast as a bioreactor to produce a large amount of the S-oxide.