Sinefungin Biosynthesis Employs a B 12 -Dependent Radical S -Adenosyl- l -methionine Enzyme Catalyzing C-Adenosylation of Arginine
Abstract
Sinefungin is a nucleoside natural product isolated from several strains of Streptomyces . The chemical structure of sinefungin is characterized by an unusual C–C bond linkage between ornithine and adenosyl fragments. Previous studies suggested that pyridoxal 5′-phosphate (PLP)-dependent enzyme catalysis is involved in the key C–C bond-forming step. Here, we show that instead of PLP catalysis, sinefungin biosynthesis involves a B 12 -dependent radical S -adenosyl- l -methionine (SAM) enzyme, SnfB, that catalyzes the C-adenosylation of arginine. The amidino group in the resulting SnfB product is then hydrolyzed by SnfC to produce sinefungin via a cryptic phosphorylation step catalyzed by SnfH. This study highlights the catalytic versatility of the B 12 -dependent radical SAM enzyme family and unveils an unconventional assembly pathway for amino acid-nucleoside conjugates in nature.
Fields of Study & Subjects
Metalloenzymes and iron-sulfur proteins
Folate and B Vitamins Research
Peptidase Inhibition and Analysis
Publication details
- Journal / source
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Volume
- 148
- Issue
- 20
- Pages
- 20343–20347
- Publication date
- 13 May 2026
- Language
- EN