Stereoselective S-oxidation of flosequinan sulfide by rat hepatic flavin-containing monooxygenase 1A1 expressed in yeast.
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.
Kashiyama
E
E
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Yokoi
T
T
Itoh
K
K
Itoh
S
S
Odomi
M
M
Kamataki
T
T
D000818:Animals; D004795:Enzyme Stability; D015870:Gene Expression; D008862:Microsomes, Liver / Q000201:enzymology*; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000378:metabolism*; D011804:Quinolines / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D013237:Stereoisomerism
D011804:Quinolines; D011994:Recombinant Proteins; C047316:flosequinan; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)