earticle

영어

The ketolides, the recent generation of antimicrobials derived semi-synthetically from the 14-membered ring macrolide erythromycin A, are characterized by possessing a 3-keto group in place of an L-cladinose group of erythromycin A. The semi-synthetic steps of ketolides involving protection and deprotection of functional groups can be shortened by combinatorial biosynthesis; namely, the employment of 5-O-desosaminyl erythronolide A (DesEA) as a precursor in the ketolide synthesis reduces the steps for the removal of L-cladinose attached at the C-3 position in erythromycin A. Deletion of an eryBV gene in an erythromycin-producer Saccharopolyspora erythraea that encodes glycosyltransferase acting on erythronolide B by attachment of L-mycarose, resulted in the accumulation of 5-O-desosaminyl erythronolide B (DesEB). In vivo expression of a gene pikC from the pikromycin biosynthetic pathway of Streptomyces venezuelae that encodes a substrate-flexible cytochrome P450 monooxygenase in the eryBV deletion mutant strain of Sac. erythraea successfully generated DesEA.