Biotin synthase: insights into radical-mediated carbon-sulfur bond formation.
The enzyme cofactor and essential vitamin biotin is biosynthesized in bacteria, fungi, and plants through a pathway that culminates with the addition of a sulfur atom to generate the five-membered thiophane ring. The immediate precursor, dethiobiotin, has methylene and methyl groups at the C6 and C9 positions, respectively, and formation of a thioether bridging these carbon atoms requires cleavage of unactivated CH bonds. Biotin synthase is an S-adenosyl-l-methionine (SAM or AdoMet) radical enzyme that catalyzes reduction of the AdoMet sulfonium to produce 5'-deoxyadenosyl radicals, high-energy carbon radicals that can directly abstract hydrogen atoms from dethiobiotin. The available experimental and structural data suggest that a [2Fe-2S](2+) cluster bound deep within biotin synthase provides a sulfur atom that is added to dethiobiotin in a stepwise reaction, first at the C9 position to generate 9-mercaptodethiobiotin, and then at the C6 position to close the thiophane ring. The formation of sulfur-containing biomolecules through a radical reaction involving an iron-sulfur cluster is an unprecedented reaction in biochemistry; however, recent enzyme discoveries suggest that radical sulfur insertion reactions may be a distinct subgroup within the burgeoning Radical SAM superfamily. This article is part of a Special Issue entitled: Radical SAM enzymes and Radical Enzymology.
Department of Chemistry, University of Hawaii at Manoa, Honolulu, HI 96822, USA.
Corey J
CJ
Fugate
Joseph T
JT
Jarrett
D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D055162:Biocatalysis; D001710:Biotin / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D002244:Carbon / Q000737:chemistry / Q000378:metabolism*; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular; D010944:Plants; D012436:S-Adenosylmethionine / Q000737:chemistry / Q000378:metabolism; D013455:Sulfur / Q000737:chemistry / Q000378:metabolism*; D013466:Sulfurtransferases / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics
D001426:Bacterial Proteins; D005609:Free Radicals; D005656:Fungal Proteins; D007506:Iron-Sulfur Proteins; D001710:Biotin; D013455:Sulfur; C004749:desthiobiotin; D002244:Carbon; D012436:S-Adenosylmethionine; D013466:Sulfurtransferases; C057985:biotin synthetase