Identification and characterization of enzymes involved in the biosynthesis of pyrimidine nucleoside antibiotics

Covering: up to September 2020 Hundreds of nucleoside-based natural products have been isolated from various microorganisms, several of which have been utilized in agriculture as pesticides and herbicides, in medicine as therapeutics for cancer and infectious disease, and as molecular probes to stud...

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Bibliographic Details
Published in:Natural product reports 2021-07, Vol.38 (7), p.1362-147
Main Authors: McErlean, M, Liu, X, Cui, Z, Gust, B, Van Lanen, S. G
Format: Article
Language:English
Subjects:
Agrochemicals
Alkylation
Anti-Bacterial Agents - metabolism
Antibiotics
Biological activity
Biological Products - metabolism
Biosynthesis
Biosynthetic Pathways
Chemical reactions
Complexity
DNA probes
Enzymes - metabolism
Herbicides
Infectious diseases
Microorganisms
Molecular Structure
Natural products
Nucleosides
Pesticides
Pyrimidine Nucleosides - biosynthesis
Scaffolds
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Summary:Covering: up to September 2020 Hundreds of nucleoside-based natural products have been isolated from various microorganisms, several of which have been utilized in agriculture as pesticides and herbicides, in medicine as therapeutics for cancer and infectious disease, and as molecular probes to study biological processes. Natural products consisting of structural modifications of each of the canonical nucleosides have been discovered, ranging from simple modifications such as single-step alkylations or acylations to highly elaborate modifications that dramatically alter the nucleoside scaffold and require multiple enzyme-catalyzed reactions. A vast amount of genomic information has been uncovered the past two decades, which has subsequently allowed the first opportunity to interrogate the chemically intriguing enzymatic transformations for the latter type of modifications. This review highlights (i) the discovery and potential applications of structurally complex pyrimidine nucleoside antibiotics for which genetic information is known, (ii) the established reactions that convert the canonical pyrimidine into a new nucleoside scaffold, and (iii) the important tailoring reactions that impart further structural complexity to these molecules. This review highlights the functional assignment and partial characterization of multiple proteins involved in the biosynthesis of structurally complex pyrimidine-derived nucleoside antibiotics.
ISSN:0265-0568
1460-4752
DOI:10.1039/d0np00064g