New Role for Radical SAM Enzymes in the Biosynthesis of Thio(seleno)oxazole RiPP Natural Products.

Ribosomally synthesized post-translationally modified peptides (RiPPs) are ubiquitous and represent a structurally diverse class of natural products. The ribosomally encoded precursor polypeptides are often extensively modified post-translationally by enzymes that are encoded by coclustered genes. Radical -adenosyl-l-methionine (SAM) enzymes catalyze numerous chemically challenging transformations.

QueE: A Radical SAM Enzyme Involved in the Biosynthesis of 7-Deazapurine Containing Natural Products.

7-Carboxy-7-deazaguanine (CDG) is a common intermediate in the biosynthesis of 7-deazapurine-containing natural products. The biosynthesis of CDG from GTP requires three enzymes: GTP cyclohydrolase I, 6-carboxy-5,6,7,8-tetrahydropterin (CPH) synthase, and CDG synthase (QueE). QueE is a member of the radical S-adenosyl-l-methionine (SAM) superfamily and catalyzes the SAM-dependent radical-mediated ring contraction of CPH to generate CDG.