ArticleChemistry & biology2015
Delineating the biosynthesis of gentamicin x2, the common precursor of the gentamicin C antibiotic complex.
Article in Chemistry & biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 77 citations in OpenAlex.
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- S-Adenosyl-d-Methionine as a Non-Physiological Substrate for a Wide Range of SAM-Dependent Enzymes.Chembiochem : a European journal of chemical biology · 2026Article
- Multifunctional Properties of the Gut Symbiont Enterococcus gallinarum Associated With Eudocima materna Caterpillars in Host Plant Detoxification.Journal of basic microbiology · 2026Article
- Insights into the stereochemical mechanism of the BCommunications biology · 2026Article
- Novel chemistry and structural perspectives in vitamin BChemical science · 2026Review
- Recent advances in the biosynthesis and production optimization of gentamicin: A critical review.Synthetic and systems biotechnology · 2025Review
- Recent advances in the biosynthetic pathway and structural modification of gentamicin.Frontiers in microbiology · 2025Review
- Structural and Functional Basis of GenB2 Isomerase Activity from Gentamicin Biosynthesis.ACS chemical biology · 2024Article
- Glycodiversification of gentamicins throughActa pharmaceutica Sinica. B · 2024Article
- Parallelized gene cluster editing illuminates mechanisms of epoxyketone proteasome inhibitor biosynthesis.Nucleic acids research · 2023Article
- Changing Fates of the Substrate Radicals Generated in the Active Sites of the BJournal of the American Chemical Society · 2023Article
- Facile and selectiveGreen chemistry : an international journal and green chemistry resource : GC · 2022Article
- Stereochemical course of cobalamin-dependent radical SAM methylation by TokK and ThnK.RSC chemical biology · 2022Article
- Characterization and utilization of methyltransferase for apramycin production in Streptoalloteichus tenebrarius.Journal of industrial microbiology & biotechnology · 2022Article
- Cobalamin-Dependent RadicalACS bio & med chem Au · 2022Review
- The Atypical Cobalamin-DependentJournal of the American Chemical Society · 2022Article
- Evolution of Methods for the Study of Cobalamin-Dependent Radical SAM Enzymes.ACS bio & med chem Au · 2022Article
- Structure of a BNature · 2022Article
- Studies of GenK and OxsB, two BMethods in enzymology · 2022Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.