The enzymology of sulfur activation during thiamin and biotin biosynthesis.

Abstract The thiamin and biotin biosynthetic pathways utilize elaborate strategies for the transfer of sulfur from cysteine to cofactor precursors. For thiamin, the sulfur atom of cysteine is transferred to a 66-amino-acid peptide (ThiS) to form a carboxy-terminal thiocarboxylate group. This sulfur transfer requires three enzymes and proceeds via a ThiS-acyladenylate intermediate. The biotin synthase Fe–S cluster functions as the immediate sulfur donor for biotin formation. C–S bond formation proceeds via radical intermediates that are generated by hydrogen atom transfer from dethiobiotin to the adenosyl radical. This radical is formed by the reductive cleavage of S -adenosylmethionine by the reduced Fe–S cluster of biotin synthase.