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Sinefungin Biosynthesis Employs a B12-Dependent Radical S-Adenosyl-l-methionine Enzyme Catalyzing C-Adenosylation of
Koki Ueno1,2, Richiro Ushimaru2,3, Yi Yang1
1Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
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 B12-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 B12-dependent radical SAM enzyme family and unveils an unconventional assembly pathway for amino acid-nucleoside conjugates in nature.
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