Identification of Genes Essential for Sulfamate and Fluorine Incorporation During Nucleocidin Biosynthesis
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Authors
Pasternak, Ola
Bechthold, Andreas
Zechel, David
Date
2022-05-11
Type
journal article
Language
en
Keyword
Biosynthesis , Fluorine , Gene Disruption , Nucleocidin , Sulfamate
Alternative Title
Abstract
Nucleocidin is an adenosine derivative containing 4’-fluoro and 5’-O-sulfamoyl substituents. In this study, nucleocidin biosynthesis is examined in two newly discovered producers, Streptomyces virens B-24331 and Streptomyces aureorectus B-24301, which produce nucleocidin and related derivatives at titres 30-fold greater than S. calvus. This enabled the identification of two new O-acetylated nucleocidin derivatives, and a potential glycosyl-O-acetyltransferase. Disruption of nucJ, nucG, and nucI, within S. virens B-24331, specifying a radical SAM/Fe-S dependent enzyme, sulfatase, and arylsulfatase, respectively, led to loss of 5’-O-sulfamoyl biosynthesis, but not fluoronucleoside production. Disruption of nucN, nucK, and nucO specifying an amidinotransferase, and two sulfotransferases respectively, led to loss of fluoronucleoside production. Identification of S. virens B-24331 as a genetically tractable and high producing strain sets the stage for understanding nucleocidin biosynthesis and highlights the utility of using 16S-RNA sequences to identify alternative producers of valuable compounds in the absence of genome sequence data.
Description
This is the peer reviewed version of the following article: A. R. O. Pasternak, A. Bechthold, D. L. Zechel, ChemBioChem 2022, e202200140, which has been published in final form at https://doi.org/10.1002/cbic.202200140. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation.
Citation
A. R. O. Pasternak, A. Bechthold, D. L. Zechel, ChemBioChem 2022, e202200140.
Publisher
Wiley