Screening of compactin-resistant microorganisms capable of converting compactin to pravastatin.
A simple method of using compactin for effective screening of microbial strains with high hydroxylation activity at the 6beta position of compactin was developed. Agar plates containing different carbon sources and 500 microg compactin mL(-1) were used to screen the microorganisms that can convert compactin to pravastatin. About 100 compactin-resistant strains were isolated from the Basal agar containing 7% (w/v) mannitol as a carbon source, in which two bacteria, Pseudomocardia autotrophica BCRC 12444 and Streptomyces griseolus BCRC 13677, capable of converting compactin to pravastatin with the yield of 20 and 32% (w/w), respectively, were found. High-performance liquid chromatography using C-18 column and two sequential mobile phases, 30% and 50% (v/v) acetonitrile, was also established to simultaneously determine the concentration of compactin and pravastatin in the culture broth. As such, about 2% of target microorganisms could be obtained from the screening program.
Chen
Chao-Hsien
CH
Department of Medical Laboratory Science, China Medical University, Taichung, 404, Taiwan.
Hu
Hui-Yu
HY
Cho
Yen-Ching
YC
Hsu
Wen-Hwei
WH
D001419:Bacteria / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media; D006900:Hydroxylation; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D017035:Pravastatin / Q000096:biosynthesis*
D003470:Culture Media; C012258:mevastatin; D008148:Lovastatin; D017035:Pravastatin