Vitamin Formation from Fatty Acid Precursors

  • Michael F. DunnEmail author
Reference work entry
Part of the Handbook of Hydrocarbon and Lipid Microbiology book series (HHLM)


Enzymes that require biotin or lipoic acid cofactors for their activity occur in all domains of life and play essential roles in metabolism. The de novo synthesis of these vitamins depends on the production of fatty acid precursors and has been most extensively characterized in Escherichia coli and Bacillus species. The octanoyl-acyl carrier protein precursor for lipoic acid is synthesized in reactions catalyzed by the fatty acid biosynthesis (Fab) enzymes. The octanoyl moiety is linked to the lipoyl domains of lipoic acid-dependent enzymes and then converted to lipoate by lipoyl synthase. For biotin biosynthesis, both the BioC-BioH pathway in E. coli and the BioI pathway in Bacillus species rely on Fab enzymes to produce the pimeloyl-acyl carrier protein required for biotin production. This review presents an overview of the biosynthetic pathways for biotin and lipoic acid, with an emphasis on the role of fatty acid metabolism in their synthesis.


  1. Beckett D (2007) Biotin sensing: universal influence of biotin status on transcription. Annu Rev Genet 41:443–464CrossRefGoogle Scholar
  2. Bi H, Zhu L, Jia J, Cronan JE (2016) A biotin biosynthesis gene restricted to Helicobacter. Sci Rep 6:21162. Scholar
  3. Bower S, Perkins JB, Yocum RR, Howitt CL, Rahaim P, Pero J (1996) Cloning, sequencing, and characterization of the Bacillus subtilis biotin biosynthetic operon. J Bacteriol 178:4122–4130CrossRefGoogle Scholar
  4. Chan DI, Vogel HJ (2010) Current understanding of fatty acid biosynthesis and the acyl carrier protein. Biochem J 430:1–19CrossRefGoogle Scholar
  5. Choi-Rhee E, Cronan JE (2005) Biotin synthase is catalytic in vivo, but catalysis engenders destruction of the protein. Chem Biol 12:461–468CrossRefGoogle Scholar
  6. Cronan JE (2014) Biotin and lipoic acid: synthesis, attachment, and regulation. EcoSal Plus. ESP-0001-2012CrossRefPubMedPubMedCentralGoogle Scholar
  7. Cronan JE (2016) Assembly of lipoic acid on its cognate enzymes: an extraordinary and essential biosynthetic pathway. Microbiol Mol Biol Rev 80:429–450CrossRefGoogle Scholar
  8. Cronan JE, Lin S (2011) Synthesis of the α, ω-dicarboxylic acid precursor of biotin by the canonical fatty acid biosynthetic pathway. Curr Opinion Chem Biol 15:407–413CrossRefGoogle Scholar
  9. Cryle MJ, Schlichting I (2008) Structural insights from a P450 carrier protein complex reveal how specificity is achieved in the P450BioI ACP complex. Proc Natl Acad Sci U S A 105:15696–15701CrossRefGoogle Scholar
  10. Dibrova DV, Galperin MY, Mulkidjanian AY (2014) Phylogenomic reconstruction of archeal fatty acid metabolism. Environ Microbiol 16:907–918CrossRefGoogle Scholar
  11. Feng Y, Cronan JE (2014) PdhR, the pyruvate dehydrogenase repressor, does not regulate lipoic acid synthesis. Res Microbiol 165:429–438CrossRefGoogle Scholar
  12. Feng Y, Napier BA, Manandhar M, Henke SK, Weiss DS, Cronan JE (2014) A Francisella virulence factor catalyzes an essential reaction of biotin biosynthesis. Mol Microbiol 91:300–314CrossRefGoogle Scholar
  13. Feng Y, Kumar R, Ravcheev DA, Zhang H (2015) Paracoccus denitrificans possesses two BioR homologs having a role in the regulation of biotin metabolism. Microbiol Open 4:644–659CrossRefGoogle Scholar
  14. Guillén-Navarro K, Encarnación S, Dunn MF (2005) Biotin biosynthesis, transport and utilization in rhizobia. FEMS Microbiol Lett 246:159–165CrossRefGoogle Scholar
  15. Janßen HJ, Steinbüchel A (2014) Fatty acid synthesis in Escherichia coli and its application towards the production of fatty acid based biofuels. Biotechnol Biofuels 7:7CrossRefGoogle Scholar
  16. Jordan SW, Cronan JE (1997) A new metabolic link. The acyl carrier protein of lipid synthesis donates lipoic acid to the pyruvate dehydrogenase complex in Escherichia coli and mitochondria. J Biol Chem 272:17903–17906CrossRefGoogle Scholar
  17. Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K (2016) KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res 45(D1):D353–D361CrossRefGoogle Scholar
  18. Lin S (2012) Biotin synthesis in Escherichia coli. PhD thesis, University of Illinois at Urbana-Champaign, 140 ppGoogle Scholar
  19. Lin S, Cronan JE (2011) Closing in on complete pathways of biotin biosynthesis. Mol BioSyst 7:1811–1821CrossRefGoogle Scholar
  20. Lin S, Cronan JE (2012) The BioC O-methyltransferase catalyzes methyl esterification of malonyl-acyl carrier protein, an essential step in biotin synthesis. J Biol Chem 287:37010–37020CrossRefGoogle Scholar
  21. Lin S, Hanson RE, Cronan JE (2010) Biotin synthesis begins by hijacking the fatty acid synthetic pathway. Nat Chem Biol 6:682–688CrossRefGoogle Scholar
  22. López-Lara IM, Geiger O (2010) Formation of fatty acids. In: Timmis KN (ed) Handbook of hydrocarbon and lipid microbiology. Springer, Berlin, pp 385–393CrossRefGoogle Scholar
  23. Martin N, Christensen QH, Mansilla MC, Cronan JE, de Mendoza D (2011) A novel two-gene requirement for the octanoyltransfer reaction of Bacillus subtilis lipoic acid biosynthesis. Mol Microbiol 80:335–349CrossRefGoogle Scholar
  24. Morris TW, Reed KE, Cronan JE Jr (1995) Lipoic acid metabolism in Escherichia coli: the lplA and lipB genes define redundant pathways for ligation of lipoyl groups to apoprotein. J Bacteriol 177:1–10CrossRefGoogle Scholar
  25. Perham RN (2000) Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions. Annu Rev Biochem 69:961–1004CrossRefGoogle Scholar
  26. Ploux O, Soularue P, Marquet A, Gloeckler R, Lemoine Y (1992) Investigation of the first step of biotin biosynthesis in Bacillus sphaericus. Biochem J 287:685–690CrossRefGoogle Scholar
  27. Qui X, Janson CA, Smith WW, Head M, Lonsdale J, Konstantinidis AK (2001) Refined structures of ß-ketoacyl-acyl carrier protein synthase III. J Mol Biol 307:341–356CrossRefGoogle Scholar
  28. Rock CO (2009) Opening a new path to lipoic acid. J Bacteriol 191:6782–6784CrossRefGoogle Scholar
  29. Rock CO, Jackowski S (2002) Forty years of bacterial fatty acid synthesis. Biochem Biophys Res Commun 292:1155–1166CrossRefGoogle Scholar
  30. Rodionov DA, Mironov AA, Gelfand MS (2002) Conservation of the biotin regulon and the BirA regulatory signal in eubacteria and Archaea. Genome Res 12:1507–1516CrossRefGoogle Scholar
  31. Satiaputra J, Shearwin KE, Booker GW, Polyak SW (2016) Mechanisms of biotin-regulated gene expression in microbes. Synth Syst Biotechnol 1:17–24CrossRefGoogle Scholar
  32. Shapiro MM, Chakravartty V, Cronan JE (2012) Remarkable diversity in the enzymes catalyzing the last step in synthesis of the pimelate moiety of biotin. PLoS One 7(11):e49440. Scholar
  33. Sohlenkamp C, Geiger O (2016) Bacterial membrane lipids: diversity in structures and pathways. FEMS Microbiol Rev 40:139–159CrossRefGoogle Scholar
  34. Stok JE, De Voss J (2000) Expression, purification, and characterization of BioI: a carbon-carbon bond cleaving cytochrome P450 involved in biotin biosynthesis in Bacillus subtilis. Arch Biochem Biophys 384:351–360CrossRefGoogle Scholar
  35. Tong L (2013) Structure and function of biotin-dependent carboxylases. Cell Mol Life Sci 70:863–891CrossRefGoogle Scholar
  36. Zhang H, Luo Q, Gao H, Feng Y (2015) A new regulatory mechanism for bacterial lipoic acid synthesis. Microbiol Open 4:282–300CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Programa de Genómica Funcional de Procariontes, Centro de Ciencias GenómicasUniversidad Nacional Autonoma de México, Av. Universidad s/n, Col. ChamilpaCuernavacaMexico

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