title: Biosynthesis of Epimers C2 and C2a in the Gentamicin C Complex.
abstract: Gentamicin is a broad-spectrum aminoglycoside antibiotic widely used to treat life-threatening bacterial infections. The gentamicin C complex consists of gentamicin C1, gentamicin C1a, and epimers gentamicin C2 and gentamicin C2a. At present there is a generally accepted pathway of gentamicin biosynthesis, except for detailed understanding of the epimerization process involving gentamicins C2 and C2a. Here we have investigated the biosynthesis of these epimers. JI-20B-an intermediate in the gentamicin biosynthetic pathway-and its epimer JI-20Ba were generated by in-frame deletion within genP, which encodes a phosphotransferase that catalyzes the first step of 3',4'-bisdehydroxylation in gentamicin biosynthesis. GenB1 and GenB2 are aminotransferases with different substrate specificities and enantioselectivities. JI-20Ba, containing a 6'S chiral amine, a precursor of gentamicin C2a, was synthesized from G418 by GenQ/GenB1 through sequential oxidation/transamination at C-6'. GenQ/GenB2 catalyzed the synthesis of JI-20B, containing a 6'R chiral amine, a precursor of gentamicin C2, from G418. GenB2 catalyzed the epimerization of JI-20Ba/JI-20B and of gentamicins C2a/C2.
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016 (P. R. China).
authors.forename: Yawen
authors.initials: Y
authors.lastname: Gu
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016 (P. R. China).
authors.forename: Xianpu
authors.initials: X
authors.lastname: Ni
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016 (P. R. China).
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.affiliation: Key Laboratory of Structure-Based Drug Design, and Discovery of Ministry of Education, School of Traditional Chinese Material Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016 (P. R. China).
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Gao
authors.affiliation: Key Laboratory of Structure-Based Drug Design, and Discovery of Ministry of Education, School of Traditional Chinese Material Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016 (P. R. China).
authors.forename: Da
authors.initials: D
authors.lastname: Wang
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016 (P. R. China).
authors.forename: Huanzhang
authors.initials: H
authors.lastname: Xia
keywords: aminoglycosides; antibiotics; biosynthesis; epimers; stereoisomerization; transamination