Discovery of the Azaserine Biosynthetic Pathway Uncovers a Biological Route for α‐Diazoester Production
- Department of Chemistry and Chemical Biology Harvard University Cambridge, MA USA
- Biological Systems and Engineering Division Lawrence Berkeley National Laboratory Berkeley, CA USA, Joint BioEnergy Institute Lawrence Berkeley National Laboratory Emeryville, CA USA
- Department of Chemistry University of California, Berkeley Berkeley, CA USA
- Biological Systems and Engineering Division Lawrence Berkeley National Laboratory Berkeley, CA USA, Joint BioEnergy Institute Lawrence Berkeley National Laboratory Emeryville, CA USA, Department of Chemical and Biomolecular Engineering University of California, Berkeley Berkeley, CA USA, Synthetic Biochemistry Center Institute for Synthetic Biology Shenzhen Institute for Advanced Technologies Shenzhen China, Center for Biosustainability Danish Technical University Lyngby Denmark
- Department of Chemistry and Chemical Biology Harvard University Cambridge, MA USA, Howard Hughes Medical Institute Harvard University Cambridge, MA USA
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.
- Research Organization:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Organization:
- USDOE; USDOE Office of Science (SC), Biological and Environmental Research (BER)
- Grant/Contract Number:
- AC02-05CH11231
- OSTI ID:
- 1975904
- Alternate ID(s):
- OSTI ID: 1975905
OSTI ID: 2234072
- Journal Information:
- Angewandte Chemie (International Edition), Journal Name: Angewandte Chemie (International Edition) Journal Issue: 28 Vol. 62; ISSN 1433-7851
- Publisher:
- Wiley Blackwell (John Wiley & Sons)Copyright Statement
- Country of Publication:
- Germany
- Language:
- English