Discovery of a Structurally Distinct Acetylenase in the Biosynthesis of Mangotoxin.

Amino acids, peptides, and proteins play pivotal roles in medicine, materials, and catalysis, with their functions largely dictated by their side-chain functionality. Recent studies have shown that heme oxygenase-like domain-containing oxidases (HDOs) catalyze a broad range of interesting chemical reactions on amino acids and their derivatives to produce structurally diverse target structures. Using a bioinformatics approach, the mangotoxin biosynthetic operon was found to house an unannotated HDO, MboA, along with a dedicated redox partner, MboB. We show that MboA catalyzes alkyne formation by iterative desaturations on the side-chain of a peptide substrate, where the transformation between alkene and alkyne is gated by MboB. The crystal structure of Fe(II)2-MboA reveals an unexpectedly short Fe-Fe distance, suggesting that the activation of strong C(sp2)-H bonds may utilize a mechanism distinct from other HDOs and expands the scope of known HDO chemistry.