Elucidation of chalkophomycin biosynthesis reveals N-hydroxypyrrole-forming enzymes.

ABSTRACT: Reactive functional groups, such as N-nitrosamines, impart unique bioactivities to the natural products in which they are found. Recent work has illuminated enzymatic N-nitrosation reactions in microbial natural product biosynthesis, motivating an interest in discovering additional metabolites constructed using such reactivity. Here, we use a genome mining approach to identify over 400 cryptic biosynthetic gene clusters (BGCs) encoding homologs of the N-nitrosating biosynthetic enzyme SznF, including the BGC for chalkophomycin, a Cu^II-binding metabolite that contains a C-type diazeniumdiolate and N-hydroxypyrrole. Characterizing chalkophomycin biosynthetic enzymes reveals previously unknown enzymes responsible for N-hydroxypyrrole biosynthesis and an unexpected role for a heme-dependent enzyme in N-nitrosation. Discovery of this pathway enriches our understanding of the biosynthetic logic employed in constructing unusual heteroatom-heteroatom bond-containing functional groups, enabling future efforts in natural product discovery and biocatalysis.

SUBMITTER: Crooke AM 

PROVIDER: S-EPMC10849742 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature