- Biosynthesis of Epimers C2 and C2a in the Gentamicin C Complex
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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.
- Gu, Yawen,Ni, Xianpu,Ren, Jun,Gao, Huiyuan,Wang, Da,Xia, Huanzhang
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p. 1933 - 1942
(2015/09/02)
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