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Complete reconstitution of the diverse pathways of gentamicin B biosynthesis

Title
Complete reconstitution of the diverse pathways of gentamicin B biosynthesis
Authors
Ban Y.H.Song M.C.Hwang J.-Y.Shin H.-L.Kim H.J.Hong S.K.Lee N.J.Park J.W.Cha S.-S.Liu H.-W.Yoon Y.J.
Ewha Authors
윤여준송명종차선신반연희
SCOPUS Author ID
윤여준scopus; 송명종scopus; 차선신scopus
Issue Date
2019
Journal Title
Nature Chemical Biology
ISSN
1552-4450JCR Link
Citation
Nature Chemical Biology vol. 15, no. 3, pp. 295 - 303
Publisher
Nature Publishing Group
Indexed
SCI; SCIE; SCOPUS scopus
Document Type
Article
Abstract
Gentamicin B (GB), a valuable starting material for the preparation of the semisynthetic aminoglycoside antibiotic isepamicin, is produced in trace amounts by the wild-type Micromonospora echinospora. Though the biosynthetic pathway to GB has remained obscure for decades, we have now identified three hidden pathways to GB production via seven hitherto unknown intermediates in M. echinospora. The narrow substrate specificity of a key glycosyltransferase and the C6′-amination enzymes, in combination with the weak and unsynchronized gene expression of the 2′-deamination enzymes, limits GB production in M. echinospora. The crystal structure of the aminotransferase involved in C6′-amination explains its substrate specificity. Some of the new intermediates displayed similar premature termination codon readthrough activity but with reduced toxicity compared to the natural aminoglycoside G418. This work not only led to the discovery of unknown biosynthetic routes to GB, but also demonstrated the potential to mine new aminoglycosides from nature for drug discovery. © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
DOI
10.1038/s41589-018-0203-4
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자연과학대학 > 화학·나노과학전공 > Journal papers
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