Dataset Information

Discovery of the Azaserine Biosynthetic Pathway Uncovers a Biological Route for α-Diazoester Production.

ABSTRACT: Azaserine is a bacterial metabolite containing a biologically unusual and synthetically enabling α-diazoester functional group. Herein, we report the discovery of the azaserine (aza) biosynthetic gene cluster from Glycomyces harbinensis. Discovery of related gene clusters reveals previously unappreciated azaserine producers, and heterologous expression of the aza gene cluster confirms its role in azaserine assembly. Notably, this gene cluster encodes homologues of hydrazonoacetic acid (HYAA)-producing enzymes, implicating HYAA in α-diazoester biosynthesis. Isotope feeding and biochemical experiments support this hypothesis. These discoveries indicate that a 2-electron oxidation of a hydrazonoacetyl intermediate is required for α-diazoester formation, constituting a distinct logic for diazo biosynthesis. Uncovering this biological route for α-diazoester synthesis now enables the production of a highly versatile carbene precursor in cells, facilitating approaches for engineering complete carbene-mediated biosynthetic transformations in vivo.

SUBMITTER: Van Cura D

PROVIDER: S-EPMC10330308 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Discovery of the Azaserine Biosynthetic Pathway Uncovers a Biological Route for α-Diazoester Production.

Van Cura Devon D Ng Tai L TL Huang Jing J Hager Harry H Hartwig John F JF Keasling Jay D JD Balskus Emily P EP

Angewandte Chemie (International ed. in English) 20230531 28

Azaserine is a bacterial metabolite containing a biologically unusual and synthetically enabling α-diazoester functional group. Herein, we report the discovery of the azaserine (aza) biosynthetic gene cluster from Glycomyces harbinensis. Discovery of related gene clusters reveals previously unappreciated azaserine producers, and heterologous expression of the aza gene cluster confirms its role in azaserine assembly. Notably, this gene cluster encodes homologues of hydrazonoacetic acid (HYAA)-pro ...[more]

PMID: 37151182

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Dataset Information

Discovery of the Azaserine Biosynthetic Pathway Uncovers a Biological Route for α-Diazoester Production.

Publications

Discovery of the Azaserine Biosynthetic Pathway Uncovers a Biological Route for α-Diazoester Production.

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