A. Pasternak, A. Bechthold, D. Zechel
May 11, 2022
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0
Influential Citations
2
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Journal
ChemBioChem
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 titers 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.