文摘
Biotransformation of mutilin and pleuromutilin by microbialcultures was investigated to provide a source of 8-hydroxymutilin or 8-hydroxypleuromutilin. LC/MS analysis of culture brothsshowed that several strains gave M+16 products from mutilinand one culture gave an M+16 product from pleuromutilin,suggesting addition of oxygen. Biotransformation products wereextracted from culture broths with ethyl acetate, dried, andpurified by chromatography on silica gel. Streptomyces griseusstrains SC 1754 and SC 13971 (ATCC 13273) converted mutilinto (8S)-, (7S)-, and (2S)-hydroxymutilin. Cunninghamella echinulata SC 16162 (NRRL 3655) gave (2S)-hydroxymutilin or (2R)-hydroxypleuromutilin from biotransformation of mutilin orpleuromutilin, respectively. The biotransformation of mutilinby S. griseus strain SC 1754 was scaled up in 15-, 60-, and 100-Lfermentations to produce a total of 49 g of (8S)-hydroxymutilin(BMS-303786), 17 g of (7S)-hydroxymutilin (BMS-303789) and13 g of (2S)-hydroxymutilin (BMS-303782) from 162 g ofmutilin.