The enzymology of sulfur activation during thiamin and biotin biosynthesis

The thiamin and biotin biosynthetic pathways utilize elaborate strategies f or the transfer of sulfur from cysteine to cofactor precursors. For thiamin , the sulfur atom of cysteine is transferred to a 66-amino-acid peptide (Th iS) 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 fo r biotin formation. C-S bond formation proceeds via radical intermediates t hat are generated by hydrogen atom transfer from dethiobiotin to the adenos yl radical. This radical is formed by the reductive cleavage of S-adenosylm ethionine by the reduced Fe-S cluster of biotin synthase.