Yawen Gu, Xianpu Ni, Jun Ren
Sep 7, 2015
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Influential Citations
26
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Journal
ChemBioChem
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.