Microbial N-demethylation: biotransformation and recovery of a drug metabolite.
A total of 39 microbes were screened for the ability to selectively N-demethylate (3R,5S,E)-7-(4-(4-fluorophenyl)-6-isopropyl-2-(methyl(1-methyl-1H-1,2,4-triazol-5-yl)aminopyrimidin-5-yl)-3,5-dihydroxy-hept-6-enoic acid (I), a potential drug for lowering blood cholesterol levels. Two Streptomyces species were found to carry out the desired N-demethylation. Bioconversion by Streptomyces griseus A.T.C.C. 13273 and product recovery were scaled up to the multi-gram level.
Davis
Brian L
BL
Process Research and Development, Bristol-Myers Squibb Co., New Brunswick, NJ 08903, USA.
Liu
Mark S
MS
Hanson
Ronald L
RL
Parker
William L
WL
Patel
Ramesh N
RN
D001419:Bacteria / Q000378:metabolism*; D001711:Biotransformation; D005658:Fungi / Q000378:metabolism*; D008745:Methylation; D011743:Pyrimidines / Q000378:metabolism*; D013302:Streptomyces / Q000378:metabolism; D014230:Triazoles / Q000378:metabolism*
C529816:7-(4-(4-fluorophenyl)-6-isopropyl-2-(methyl(1-methyl-1H-1,2,4-triazol-5-yl)amino)pyrimidin-5-yl)-3,5-dihydroxyhept-6-enoic acid; D011743:Pyrimidines; D014230:Triazoles