Enzymology of carbon-sulfur bond formation.

Mobilization of the sulfur of cysteine as persulfide is the first step of sulfur transfer into thiamin, molydopterin, 4-thiouridine, biotin and lipoic acid, but then the pathways diverge completely. For the first three compounds, one or several proteinic persulfides are involved, ending in the nucleophilic attack of a sulfur, persulfide, sulfide or thiocarboxylate on a carbonyl equivalent. Several proteins have been newly characterized, revealing homologies between the three biosynthetic routes and evolutionary relationships. In the case of biotin, and very probably of lipoic acid, the sulfur is transferred as sulfide into the [Fe-S] center of the enzyme. This [Fe-S] center is the ultimate sulfur donor, which quenches a carbon radical on the substrate. This radical is produced by homolytic cleavage of a C-H bond by a deoxyadenosyl radical arising from the reduction of S-adenosylmethionine.