Leeper Group



Part of biosynthetic pathway Junhong Guo, Fanglu Huang, Chuan Huang, Xiaobo Duan, Xinyun Jian, Finian J. Leeper, Zixin Deng, Peter F. Leadlay and Yuhui Sun
"Specificity and Promiscuity at the Branch Point in Gentamicin Biosynthesis"
Chem. & Biol., 2014, 21 (5), 608618. Full Text.

Gentamicin C complex is a mixture of aminoglycoside antibiotics used to treat severe Gram-negative bacterial infections. We report here key features of the late-stage biosynthesis of gentamicins. We show that the intermediate gentamicin X2, a known substrate for C-methylation at C-6' to form G418 catalyzed by the radical SAM-dependent enzyme GenK, may instead undergo oxidation at C-6' to form an aldehyde, catalyzed by the flavin-linked dehydrogenase GenQ. Surprisingly, GenQ acts in both branches of the pathway, likewise oxidizing G418 to an analogous ketone. Amination of these intermediates, catalyzed mainly by aminotransferase GenB1, produces the known intermediates JI-20A and JI-20B, respectively. Other pyridoxal phosphate-dependent enzymes (GenB3 and GenB4) act in enigmatic dehydroxylation steps that convert JI-20A and JI-20B into the gentamicin C complex or (GenB2) catalyze the epimerization of gentamicin C2a into gentamicin C2.

Previous abstract Next abstract


Department of Chemistry
University of Cambridge