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Methyltransferases of gentamicin biosynthesis.

Abstract：

:Gentamicin C complex from Micromonospora echinospora remains a globally important antibiotic, and there is revived interest in the semisynthesis of analogs that might show improved therapeutic properties. The complex consists of five components differing in their methylation pattern at one or more sites in the molecule. We show here, using specific gene deletion and chemical complementation, that the gentamicin pathway up to the branch point is defined by the selectivity of the methyltransferases GenN, GenD1, and GenK. Unexpectedly, they comprise a methylation network in which early intermediates are ectopically modified. Using whole-genome sequence, we have also discovered the terminal 6'-N-methyltransfer required to produce gentamicin C2b from C1a or gentamicin C1 from C2, an example of an essential biosynthetic enzyme being located not in the biosynthetic gene cluster but far removed on the chromosome. These findings fully account for the methylation pattern in gentamicins and open the way to production of individual gentamicins by fermentation, as starting materials for semisynthesis.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Li S,Guo J,Reva A,Huang F,Xiong B,Liu Y,Deng Z,Leadlay PF,Sun Y

doi

10.1073/pnas.1711603115

subject

Has Abstract

pub_date

2018-02-06 00:00:00

pages

1340-1345

issue

6

eissn

0027-8424

issn

1091-6490

pii

1711603115

journal_volume

115

pub_type

杂志文章

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