EC - Biotin synthase

  IntEnz view ENZYME view

IntEnz Enzyme Nomenclature


Accepted name:
biotin synthase
Other name:
dethiobiotin:sulfur sulfurtransferase
Systematic name:
dethiobiotin:sulfur-(sulfur carrier) sulfurtransferase




The enzyme binds a [4Fe-4S] and a [2Fe-2S] cluster. In every reaction cycle, the enzyme consumes two molecules of AdoMet, each producing 5'-deoxyadenosine and a putative dethiobiotinyl carbon radical. Reaction with another equivalent of AdoMet results in abstraction of the C6 methylene pro-S hydrogen atom from 9-mercaptodethiobiotin, and the resulting carbon radical is quenched via formation of an intramolecular C-S bond, thus closing the biotin thiophane ring. The sulfur donor is believed to be the [2Fe-2S] cluster, which is sacrificed in the process, so that in vitro the reaction is a single turnover. In vivo, the [2Fe-2S] cluster can be reassembled by the Isc or Suf iron-sulfur cluster assembly systems, to allow further catalysis.

Links to other databases

Enzymes and pathways: NC-IUBMB , BRENDA , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , UniPathway
Structural data: CSA , EC2PDB
Gene Ontology: GO:0004076
CAS Registry Number: 80146-93-6
UniProtKB/Swiss-Prot: (592) [show] [UniProt]


  1. Shiuan, D. and Campbell, A.
    Transcriptional regulation and gene arrangement of Escherichia coli, Citrobacter freundii and Salmonella typhimurium biotin operons.
    Gene 67: 203-211 (1988). [PMID: 2971595]
  2. Zhang, S., Sanyal, I., Bulboaca, G.H., Rich, A. and Flint, D.H.
    The gene for biotin synthase from Saccharomyces cerevisiae: cloning, sequencing, and complementation of Escherichia coli strains lacking biotin synthase.
    Arch. Biochem. Biophys. 309: 29-35 (1994). [PMID: 8117110]
  3. Trainor, D.A., Parry, R.J. and Gitterman, A.
    Biotin biosynthesis. 2. Stereochemistry of sulfur introduction at C-4 of dethiobiotin.
    J. Am. Chem. Soc. 102: 1467-1468 (1980).
  4. Lotierzo, M., Tse Sum Bui, B., Florentin, D., Escalettes, F. and Marquet, A.
    Biotin synthase mechanism: an overview.
    Biochem. Soc. Trans. 33: 820-823 (2005). [PMID: 16042606]
  5. Berkovitch, F., Nicolet, Y., Wan, J.T., Jarrett, J.T. and Drennan, C.L.
    Crystal structure of biotin synthase, an S-adenosylmethionine-dependent radical enzyme.
    Science 303: 76-79 (2004). [PMID: 14704425]
  6. Ugulava, N.B., Gibney, B.R. and Jarrett, J.T.
    Biotin synthase contains two distinct iron-sulfur cluster binding sites: chemical and spectroelectrochemical analysis of iron-sulfur cluster interconversions.
    Biochemistry 40: 8343-8351 (2001). [PMID: 11444981]
  7. Taylor, A. M., Farrar, C. E., Jarrett, J. T.
    9-Mercaptodethiobiotin is formed as a competent catalytic intermediate by Escherichia coli biotin synthase.
    Biochemistry 47: 9309-9317 (2008). [PMID: 18690713]
  8. Reyda, M. R., Fugate, C. J., Jarrett, J. T.
    A complex between biotin synthase and the iron-sulfur cluster assembly chaperone HscA that enhances in vivo cluster assembly.
    Biochemistry 48: 10782-10792 (2009). [PMID: 19821612]

[EC created 1999, modified 2006, modified 2011, modified 2014]