Biotin synthase is a pyridoxal phosphate-dependent cysteine desulfurase

Biochemistry. 2002 Jul 23;41(29):9145-52. doi: 10.1021/bi0122011.


Biotin synthase (BioB) is an iron-sulfur dimeric enzyme which catalyzes the last step in biotin synthesis. The reaction consists of the introduction of a sulfur atom into dethiobiotin. It is shown here that BioB displays a significant cysteine desulfurase activity, providing it with the ability to mobilize sulfur from free cysteine. This activity is dependent on pyridoxal 5'-phosphate (PLP) and dithiothreitol and proceeds through a protein-bound persulfide. Like other cysteine desulfurases, BioB binds 1 equiv of PLP. By site-directed mutagenesis, two conserved cysteines, Cys97 and Cys128, are shown to be critical for cysteine desulfuration and are good candidates as the site for a persulfide. Since biotin synthase activity is greatly increased by PLP and cysteine, even though it does not exceed 1 nmol of biotin/nmol of monomer, it is proposed that cysteine desulfuration is intimately linked to biotin synthesis. New scenarios for sulfur insertion into dethiobiotin, in which cysteine persulfides play a key role, are discussed.

MeSH terms

  • Carbon-Sulfur Lyases*
  • Catalysis
  • Lyases / genetics
  • Lyases / metabolism*
  • Mutagenesis, Site-Directed
  • Pyridoxal Phosphate / metabolism*
  • Recombinant Proteins / metabolism
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrophotometry, Ultraviolet
  • Sulfurtransferases / genetics
  • Sulfurtransferases / metabolism*


  • Recombinant Proteins
  • Pyridoxal Phosphate
  • Sulfurtransferases
  • biotin synthetase
  • Lyases
  • Carbon-Sulfur Lyases
  • cysteine desulfurase