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B6db references: 30643280

type Journal Article
authors Ban YH, Song MC, Hwang JY, Shin HL, Kim HJ, Hong SK, Lee NJ, Park JW, Cha SS, Liu HW, Yoon YJ
title Complete reconstitution of the diverse pathways of gentamicin B biosynthesis
journal Nat Chem Biol
Activity genb1
Family genb1
sel selected
ui 30643280
year (2019)
volume 15
number 3
pages 295-303
keywords doi: 10.1038/s41589-018-0203-4
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.
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last changed 2019/03/12 09:53

B6db references