Issue 41, 2019

Two 3′-O-β-glucosylated nucleoside fluorometabolites related to nucleocidin in Streptomyces calvus

Abstract

The antibiotic nucleocidin is a product of the soil bacterium Streptomyces calvus T-3018. It is among the very rare fluorine containing natural products but is distinct from the other fluorometabolites in that it is not biosynthesised from 5′-fluorodeoxyadenosine via the fluorinase. It seems to have a unique enzymatic fluorination process. We disclose here the structures of two 4′-fluoro-3′-O-β-glucosylated metabolites (F-Mets I and II) which appear and then disappear before nucleocidin production in batch cultures of S. calvus. Full genome sequencing of S. calvus T-3018 and an analysis of the putative biosynthetic gene cluster for nucleocidin identified UDP-glucose dependent glucosyl transferase (nucGT) and glucosidase (nucGS) genes within the cluster. We demonstrate that these genes express enzymes that have the capacity to attach and remove glucose from the 3′-O-position of adenosine analogues. In the case of F-Met II, deglucosylation with the NucGS glucosidase generates nucleocidin suggesting a role in its biosynthesis. Gene knockouts of nucGT abolished nucelocidin production.

Graphical abstract: Two 3′-O-β-glucosylated nucleoside fluorometabolites related to nucleocidin in Streptomyces calvus

Supplementary files

Article information

Article type
Edge Article
Submitted
08 Jul 2019
Accepted
19 Aug 2019
First published
20 Aug 2019
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2019,10, 9501-9505

Two 3′-O-β-glucosylated nucleoside fluorometabolites related to nucleocidin in Streptomyces calvus

X. Feng, D. Bello, P. T. Lowe, J. Clark and D. O'Hagan, Chem. Sci., 2019, 10, 9501 DOI: 10.1039/C9SC03374B

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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