Identification of Genes Essential for Sulfamate and Fluorine Incorporation During Nucleocidin Biosynthesis.

biosynthesis fluorine gene disruption nucleocidin sulfamate

Journal

Chembiochem : a European journal of chemical biology
ISSN: 1439-7633
Titre abrégé: Chembiochem
Pays: Germany
ID NLM: 100937360

Informations de publication

Date de publication:
03 08 2022
Historique:
revised: 05 05 2022
received: 10 03 2022
pubmed: 12 5 2022
medline: 6 8 2022
entrez: 11 5 2022
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 35544615
doi: 10.1002/cbic.202200140
doi:

Substances chimiques

Sulfonic Acids 0
Fluorine 284SYP0193
sulfamic acid 9NFU33906Q
Sulfatases EC 3.1.6.-
nucleocidin F5097NG7JT
Adenosine K72T3FS567

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e202200140

Informations de copyright

© 2022 Wiley-VCH GmbH.

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Auteurs

A R Ola Pasternak (ARO)

Department of Chemistry, Queen's University, 90 Bader Ln, Kingston, ON K7L 2S8, Canada.

Andreas Bechthold (A)

Department of Pharmaceutical Biology and Biotechnology, Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Stefan-Meier-Str. 19, 79104, Freiburg i. Br., Germany.

David L Zechel (DL)

Department of Chemistry, Queen's University, 90 Bader Ln, Kingston, ON K7L 2S8, Canada.

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