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.