|
type |
Journal Article |
authors |
Huang C, Huang F, Moison E, Guo J, Jian X, Duan X, Deng Z, Leadlay PF, Sun Y. |
title |
Delineating the biosynthesis of gentamicin x2, the common precursor of the gentamicin C antibiotic complex. |
journal |
Chem Biol. |
Activity |
gens2 |
Family |
gens2 |
sel |
selected |
ui |
25641167 |
year |
(2015) |
volume |
22 |
number |
2 |
pages |
251-261 |
| |
abstract |
Gentamicin C complex is a mixture of aminoglycoside antibiotics used worldwide to treat severe Gram-negative bacterial infections. Despite its clinical importance, the enzymology of its biosynthetic pathway has remained obscure. We report here insights into the four enzyme-catalyzed steps that lead from the first-formed pseudotrisaccharide gentamicin A2 to gentamicin X2, the last common intermediate for all components of the C complex. We have used both targeted mutations of individual genes and reconstitution of portions of the pathway in vitro to show that the secondary alcohol function at C-3″ of A2 is first converted to an amine, catalyzed by the tandem operation of oxidoreductase GenD2 and transaminase GenS2. The amine is then specifically methylated by the S-adenosyl-l-methionine (SAM)-dependent N-methyltransferase GenN to form gentamicin A. Finally, C-methylation at C-4″ to form gentamicin X2 is catalyzed by the radical SAM-dependent and cobalamin-dependent enzyme GenD1. |
last changed |
2018/03/27 09:53 |
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