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Biosynthetic Plasticity Enables Production of Fluorinated Aurachins.

ABSTRACT: Enzyme promiscuity has important implications in the field of biocatalysis. In some cases, structural analogues of simple metabolic building blocks can be processed through entire pathways to give natural product derivatives that are not readily accessible by chemical means. In this study, we explored the plasticity of the aurachin biosynthesis pathway with regard to using fluoro- and chloroanthranilic acids, which are not abundant in the bacterial producers of these quinolone antibiotics. The incorporation rates of the tested precursor molecules disclosed a regiopreference for halogen substitution as well as steric limitations of enzymatic substrate tolerance. Three previously undescribed fluorinated aurachin derivatives were produced in preparative amounts by fermentation and structurally characterized. Furthermore, their antibacterial activities were evaluated in comparison to their natural congener aurachin D.

SUBMITTER: Sester A

PROVIDER: S-EPMC7496329 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Biosynthetic Plasticity Enables Production of Fluorinated Aurachins.

Sester Angela A Stüer-Patowsky Katrin K Hiller Wolf W Kloss Florian F Lütz Stephan S Nett Markus M

Chembiochem : a European journal of chemical biology 20200505 16

Enzyme promiscuity has important implications in the field of biocatalysis. In some cases, structural analogues of simple metabolic building blocks can be processed through entire pathways to give natural product derivatives that are not readily accessible by chemical means. In this study, we explored the plasticity of the aurachin biosynthesis pathway with regard to using fluoro- and chloroanthranilic acids, which are not abundant in the bacterial producers of these quinolone antibiotics. The i ...[more]

PMID: 32216075

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