Membrane Formation and Regulation

  • Megan E. Ericson
  • Charles O. RockEmail author
Reference work entry
Part of the Handbook of Hydrocarbon and Lipid Microbiology book series (HHLM)


Membrane homeostasis in bacteria ensures survival in rapidly changing environments. Most prokaryotes utilize the essential type II fatty acid synthesis to generate lipid species required for membrane formation and adaptation. This highly conserved system consists of multiple enzymes that each catalyzes a specific reaction. FAS II is an energy-intensive process and regulatory control at both transcriptional and biochemical levels ensuring the pathway output matches the demand for new membrane. This review summarizes the steps of FASII, the key regulatory steps, and checks and balances that maintain membrane homeostasis.



This work was supported by the National Institutes of Health Grants GM034496 (C.O.R.), Cancer Center Support Grant CA21765, and the American Lebanese Syrian Associated Charities.


  1. Battesti A, Bouveret E (2006) Acyl carrier protein/SpoT interaction, the switch linking SpoT-dependent stress response to fatty acid metabolism. Mol Microbiol 62(4):1048–1063CrossRefGoogle Scholar
  2. Bi H, Wang H, Cronan JE (2013) FabQ, a dual-function dehydratase/isomerase, circumvents the last step of the classical fatty acid synthesis cycle. Chem Biol 20(9):1157–1167CrossRefGoogle Scholar
  3. Bredenbruch F, Nimtz M, Wray V, Morr M, Muller R, Haussler S (2005) Biosynthetic pathway of Pseudomonas aeruginosa 4-hydroxy-2-alkylquinolines. J Bacteriol 187(11):3630–3635CrossRefGoogle Scholar
  4. Cronan JE Jr (2003) Bacterial membrane lipids: where do we stand? Annu Rev Microbiol 57:203–224CrossRefGoogle Scholar
  5. Cronan JE Jr, Waldrop GL (2002) Multi-subunit acetyl-CoA carboxylases. Prog Lipid Res 41(5):407–435CrossRefGoogle Scholar
  6. Davis MS, Cronan JE Jr (2001) Inhibition of Escherichia coli acetyl coenzyme A carboxylase by acyl-acyl carrier protein. J Bacteriol 183:1499–1503CrossRefGoogle Scholar
  7. Davis MS, Solbiati J, Cronan JE Jr (2000) Overproduction of acetyl-CoA carboxylase activity increases the rate of fatty acid biosynthesis in Escherichia coli. J Biol Chem 275(37):28593–28598CrossRefGoogle Scholar
  8. Grogan DW, Cronan JE Jr (1997) Cyclopropane ring formation in membrane lipids of bacteria. Microbiol Mol Biol Rev 61(4):429–441PubMedPubMedCentralGoogle Scholar
  9. Heath RJ, Rock CO (1995) Regulation of malonyl-CoA metabolism by acyl-acyl carrier protein and b-ketoacyl-acyl carrier protein synthases in Escherichia coli. J Biol Chem 270:15531–15538CrossRefGoogle Scholar
  10. Heath RJ, Rock CO (1996) Regulation of fatty acid elongation and initiation by acyl-acyl carrier protein in Escherichia coli. J Biol Chem 271:1833–1836CrossRefGoogle Scholar
  11. Janssen HJ, Steinbüchel A (2014) Fatty acid synthesis in Escherichia coli and its applications towards the production of fatty acid based biofuels. Biotechnol Biofuels 7(1):7CrossRefGoogle Scholar
  12. Jordan SW, Cronan JE Jr (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
  13. Kanfer J, Kennedy EP (1964) Metabolism and function of bacterial lipids II. Biosynthesis of phospholipids in Escherichia coli. J Biol Chem 239:1720–1726PubMedGoogle Scholar
  14. Li Y, Florova G, Reynolds KA (2005) Alteration of the fatty acid profile of Streptomyces coelicolor by replacement of the initiation enzyme 3-ketoacyl acyl carrier protein synthase III (FabH). J Bacteriol 187(11):3795–3799CrossRefGoogle Scholar
  15. Lin S, Hanson RE, Cronan JE (2010) Biotin synthesis begins by hijacking the fatty acid synthetic pathway. Nat Chem Biol 6(9):682–688CrossRefGoogle Scholar
  16. Lu Y-J, Rock CO (2006) Transcriptional regulation of fatty acid biosynthesis in Streptococcus pneumoniae. Mol Microbiol 59:551–566CrossRefGoogle Scholar
  17. Lu Y-J, Zhang Y-M, Rock CO (2004) Product diversity and regulation of type II fatty acid synthases. Biochem Cell Biol 82:145–155CrossRefGoogle Scholar
  18. Lu Y-J, Zhang Y-M, Grimes KD, Qi J, Lee RE, Rock CO (2006) Acyl-phosphates initiate membrane phospholipid synthesis in gram-positive pathogens. Mol Cell 23(5):765–772CrossRefGoogle Scholar
  19. Mansilla MC, de Mendoza D (2005) The Bacillus subtilis desaturase: a model to understand phospholipid modification and temperature sensing. Arch Microbiol 183(4):229–235CrossRefGoogle Scholar
  20. Mantsch HH, Madec C, Lewis RNAH, McElhaney RN (1985) Thermotropic phase behavior of model membranes composed of phosphatidylcholine containing iso-branched fatty acids. 2. Infrared and 31P NMR spectroscopic studies. Biochemistry 24:2440–2446CrossRefGoogle Scholar
  21. Marrakchi H, Zhang Y-M, Rock CO (2002) Mechanistic diversity and regulation of type II fatty acid synthesis. Biochem Soc Trans 30:1050–1055CrossRefGoogle Scholar
  22. More MI, Finger LD, Stryker JL, Fuqua C, Eberhard A, Winans SC (1996) Enzymatic synthesis of a quorum-sensing autoinducer through use of defined substrates. Science 272(5268):1655–1658CrossRefGoogle Scholar
  23. Paoletti L, Lu Y-J, Schujman GE, de Mendoza D, Rock CO (2007) Coupling of fatty acid and phospholipid synthesis in Bacillus subtilis. J Bacteriol 189:5816–5824CrossRefGoogle Scholar
  24. Parsons JB, Rock CO (2011) Is bacterial fatty acid synthesis a valid target for antibacterial drug discovery? Curr Opin Microbiol 14:544–549CrossRefGoogle Scholar
  25. Parsons JB, Rock CO (2013) Bacterial lipids: metabolism and membrane homeostasis. Prog Lipid Res 52:249–276CrossRefGoogle Scholar
  26. Parsons JB, Frank MW, Subramanian C, Saenkham P, Rock CO (2011) Metabolic basis for the differential susceptibility of Gram-positive pathogens to fatty acid synthesis inhibitors. Proc Natl Acad Sci U S A 108(37):15378–15383CrossRefGoogle Scholar
  27. Parsons JB, Broussard TC, Bose JL, Rosch JW, Jackson P, Subramanian C, Rock CO (2014) Identification of a two-component fatty acid kinase responsible for host fatty acid incorporation by Staphylococcus aureus. Proc Natl Acad Sci U S A 111:10532–10537CrossRefGoogle Scholar
  28. Raetz CR, Reynolds CM, Trent MS, Bishop RE (2007) Lipid A modification systems in Gram-negative bacteria. Annu Rev Biochem 76:295–329CrossRefGoogle Scholar
  29. Schujman GE, Paoletti L, Grossman AD, de Mendoza D (2003) FapR, a bacterial transcription factor involved in global regulation of membrane lipid biosynthesis. Dev Cell 4(5):663–672CrossRefGoogle Scholar
  30. White SW, Zheng J, Zhang Y-M, Rock CO (2005) The structural biology of type II fatty acid biosynthesis. Annu Rev Biochem 74:791–831CrossRefGoogle Scholar
  31. Yao J, Rock CO (2013) Phosphatidic acid synthesis in bacteria. Biochim Biophys Acta 1831(3):495–502CrossRefGoogle Scholar
  32. Yuan Y, Schdeva M, Leeds JA, Meredith TC (2012) Fatty acid biosynthesis in Pseudomonas aeruginosa is initiated by FabY: a new class of b-ketoacyl-acyl carrier protein synthases. J Bacteriol 194(19):5171–5184CrossRefGoogle Scholar
  33. Zhang Y-M, Rock CO (2008) Membrane lipid homeostasis in bacteria. Nat Rev Microbiol 6:222–233CrossRefGoogle Scholar
  34. Zhang Y-M, Rock CO (2009) Transcriptional regulation in bacterial membrane lipid synthesis. J Lipid Res 50:S115–S119CrossRefGoogle Scholar
  35. Zhang Y-M, Rock CO (2015) Fatty acid and phospholipid biosynthesis in prokaryotes. In: Ridgway ND, RS ML (eds) Biochemistry of Lipids, Lipoproteins and Membranes, 6th edn. Elsevier, Amsterdam, pp 73–112Google Scholar
  36. Zhang Y-M, Marrakchi H, White SW, Rock CO (2003) The application of computational methods to explore the diversity and structure of bacterial fatty acid synthase. J Lipid Res 44:1–10CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Infectious DiseasesSt. Jude Children’s Research HospitalMemphisUSA

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