title: 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.
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA. tpb2@cornell.edu.
authors.forename: T P
authors.initials: TP
authors.lastname: Begley
authors.forename: J
authors.initials: J
authors.lastname: Xi
authors.forename: C
authors.initials: C
authors.lastname: Kinsland
authors.forename: S
authors.initials: S
authors.lastname: Taylor
authors.forename: F
authors.initials: F
authors.lastname: McLafferty
mesh_terms: D001710:Biotin / Q000096:biosynthesis*; D003545:Cysteine / Q000378:metabolism; D008956:Models, Chemical; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D013455:Sulfur / Q000378:metabolism*; D013466:Sulfurtransferases / Q000378:metabolism; D013831:Thiamine / Q000096:biosynthesis*
chemical_list: D001710:Biotin; D013455:Sulfur; D017853:Phosphotransferases (Alcohol Group Acceptor); C035182:thiamin kinase; D013466:Sulfurtransferases; C057985:biotin synthetase; D003545:Cysteine; D013831:Thiamine