Revision of the Formycin A and Pyrazofurin Biosynthetic Pathways Reveals Specificity for d-Glutamic Acid and a Cryptic <i>N</i>-Acylation Step During Pyrazole Core Formation.

ABSTRACT: Formycin A and pyrazofurin are two naturally occurring pyrazole-derived C-nucleosides with antibacterial and antiviral activities. While earlier studies have established the chemistry of C-glycosidic bond formation as well as the subsequent steps in the biosynthesis of formycin A and pyrazofurin, how the pyrazole ring itself is constructed remains elusive. While N-N bond formation in the pyrazole ring was previously reported to involve coupling of N⁶-hydroxylated l-lysine and l-glutamic acid catalyzed by the hydrazine synthetase PyfG, herein PyfG and its homologue ForJ are shown instead to recognize d-glutamate instead of l-glutamate. The hydrazine product of ForJ/PyfG catalysis then releases α-hydrazino d-glutamic acid upon processing by the NAD-dependent o

SUBMITTER: Zheng Z 

PROVIDER: S-EPMC11964824 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature