Biotin synthesis begins by hijacking the fatty acid synthetic pathway

Nat Chem Biol. 2010 Sep;6(9):682-8. doi: 10.1038/nchembio.420. Epub 2010 Aug 8.


Although biotin is an essential enzyme cofactor found in all three domains of life, our knowledge of its biosynthesis remains fragmentary. Most of the carbon atoms of biotin are derived from pimelic acid, a seven-carbon dicarboxylic acid, but the mechanism whereby this intermediate is assembled remains unknown. Genetic analysis in Escherichia coli identified only two genes of unknown function required for pimelate synthesis, bioC and bioH. We report in vivo and in vitro evidence that the pimeloyl moiety is synthesized by a modified fatty acid synthetic pathway in which the omega-carboxyl group of a malonyl-thioester is methylated by BioC, which allows recognition of this atypical substrate by the fatty acid synthetic enzymes. The malonyl-thioester methyl ester enters fatty acid synthesis as the primer and undergoes two reiterations of the fatty acid elongation cycle to give pimeloyl-acyl carrier protein (ACP) methyl ester, which is hydrolyzed to pimeloyl-ACP and methanol by BioH.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acyl Carrier Protein / metabolism
  • Biotin / antagonists & inhibitors
  • Biotin / biosynthesis*
  • Biotin / genetics
  • Biotin / metabolism
  • Dose-Response Relationship, Drug
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Esters / chemistry
  • Esters / metabolism
  • Fatty Acid Synthesis Inhibitors / pharmacology
  • Fatty Acids / biosynthesis*
  • Fatty Acids / metabolism
  • Hydrolysis
  • Methanol / chemistry
  • Methanol / metabolism
  • Methylation
  • Substrate Specificity
  • Vibrio


  • Acyl Carrier Protein
  • Esters
  • Fatty Acid Synthesis Inhibitors
  • Fatty Acids
  • Biotin
  • Methanol