Regulation of Fatty Acids Degradation in Bacteria

  • Lorena Jimenez-DiazEmail author
  • Antonio Caballero
  • Ana Segura
Reference work entry
Part of the Handbook of Hydrocarbon and Lipid Microbiology book series (HHLM)


Fatty acids occupy a central role in bacterial metabolism; they serve as an energy reservoir, as integral components of the membrane, and as signal molecules. As such, their biosynthesis and degradation pathways are tightly regulated. This regulation is controlled directly; for example, in the presence of free fatty acids, the global FadR regulator derepresses genes that encode fatty acid transport and degradation proteins. Fatty acid pathways are also regulated indirectly. This is because Fad genes respond in an integrated manner to different environmental cues. In Escherichia coli, expression of the Fad genes is modulated by (i) the carbon source, mediated by the catabolic repression protein CRP; (ii) oxygen levels, mediated through the ArcA/ArcB two-component system; (iii) osmotic stress, mediated by the EnvZ-OmpR system; and (iv) the physiological status of the cell, mediated by RpoS and ppGpp through direct and indirect mechanisms. In addition to this transcriptional regulation, the glyoxylate shunt is also regulated at the protein level by the phosphorylation of the isocitrate dehydrogenase. This complex network of regulation emphasizes the importance of maintaining the appropriate types and levels of fatty acids according to physiological and environmental conditions and the relevance of fatty acid modulation during the stress response.



This work was funded by Abengoa Research.

We thank Ben Pakuts for editing the manuscript.


  1. Bacik J-P, Yeager CM, Twary SN, Martí-Arbona R (2015) Modulation of FadR binding capacity for acyl-CoA fatty acids through structure-guided mutagenesis. Protein J 34:359–366PubMedCrossRefGoogle Scholar
  2. Battesti A, Majdalani N, Gottesman S (2011) The RpoS-mediated general stress response in Escherichia coli. Annu Rev Microbiol 65:189–213PubMedCrossRefGoogle Scholar
  3. Black PN, DiRusso CC (1994) Molecular and biochemical analyses of fatty acid transport, metabolism, and gene regulation in Escherichia coli. Biochim Biophys Acta 1210:123–145PubMedCrossRefGoogle Scholar
  4. Black PN, Dirusso CC, Metzger AK, Heimert TL (1992) Cloning, sequencing, and expression of the fadD gene of Escherichia coli encoding acyl coenzyme-A synthetase. J Biol Chem 267:25513–25520PubMedGoogle Scholar
  5. Borthwick AC, Holms WH, Nimmo HG (1984) The phosphorylation of Escherichia coli isocitrate dehydrogenase in intact cells. Biochem J 222:797–804PubMedPubMedCentralCrossRefGoogle Scholar
  6. Bradley MD, Beach MB, de Koning APJ, Pratt TS, Osuna R (2007) Effects of Fis on Escherichia coli gene expression during different growth stages. Microbiology 153:2922–2940PubMedCrossRefGoogle Scholar
  7. Campbell JW, Cronan JE Jr (2001) Escherichia coli FadR positively regulates transcription of the fabB fatty acid biosynthetic gene. J Bacteriol 183:5982–5990PubMedPubMedCentralCrossRefGoogle Scholar
  8. Campbell JW, Morgan-Kiss RM, Cronan JE (2003) A new Escherichia coli metabolic competency: growth on fatty acids by a novel anaerobic β-oxidation pathway. Mol Microbiol 47:793–805. Scholar
  9. Cho BK, Knight EM, Palsson BØ (2006) Transcriptional regulation of the fad regulon genes of Escherichia coli by ArcA. Microbiology 152:2207–2219PubMedCrossRefGoogle Scholar
  10. Clark DP, Cronan JE (2005) Two-carbon compounds and fatty acids as carbon sources. EcoSal Plus Cell Mol Biol 1:1–34Google Scholar
  11. Clark DP, DeMendoza D, Polacco ML, Cronan JE Jr (1983) β-hydroxydecanoyl thio ester dehydrase does not catalyze a rate-limiting step in Escherichia coli unsaturated fatty acid synthesis. Biochemistry 22:5897–5902PubMedCrossRefGoogle Scholar
  12. Cortay JC, Nègre D, Galinier A, Duclos B, Perrière G, Cozzone AJ (1991) Regulation of the acetate operon in Escherichia coli: purification and functional characterization of the IclR repressor. EMBO J 10:675–679PubMedPubMedCentralCrossRefGoogle Scholar
  13. Cronan JE Jr, Gelmann EP (1975) Physical properties of membrane lipids: biological relevance and regulation. Bacterial. Rev 39:232–256Google Scholar
  14. Cronan JE, Laporte D (2006) Tricarboxylic acid cycle and glyoxylate bypass. EcoSal Plus 1:1–26. Scholar
  15. Cronan JE, Subrahmanyam S (1998) FadR, transcriptional co-ordination of metabolic expediency. Mol Microbiol 29:937–943PubMedCrossRefGoogle Scholar
  16. Dalebroux ZD, Swanson MS (2012) ppGpp: magic beyond RNA polymerase. Nat Rev Microbiol 10:203–212PubMedCrossRefGoogle Scholar
  17. Dean AM, Lee MHI, Koshland DE (1989) Phosphorylation inactivates Escherichia coli isocitrate dehydrogenase by preventing isocitrate binding. J Biol Chem 264:20482–20486PubMedGoogle Scholar
  18. DiRusso CC, Heimert TL, Metzger AK (1992) Characterization of FadR, a global transcriptional regulator of fatty acid metabolism in Escherichia coli. Interaction with the fadB promoter is prevented by long chain fatty acyl coenzyme A. J Biol Chem 267:8685–8691PubMedGoogle Scholar
  19. DiRusso CC, Metzger AK, Heimert TL (1993) Regulation of transcription of genes required for fatty acid transport and unsaturated fatty acid biosynthesis in Escherichia coli by FadR. Mol Microbiol 7:311–322PubMedCrossRefGoogle Scholar
  20. DiRusso CC, Tsvetnitsky V, Hojrup P, Knudsen J (1998) Fatty acyl-CoA binding domain of the transcription factor FadR. Characterization by deletion, affinity labeling, and isothermal titration calorimetry. J Biol Chem 273:33652–33659PubMedCrossRefGoogle Scholar
  21. Dong T, Schellhorn HE (2009a) Control of RpoS in global gene expression of Escherichia coli in minimal media. Mol Genet Genomics 281(1):19–33PubMedCrossRefGoogle Scholar
  22. Dong T, Schellhorn HE (2009b) Global effect of RpoS on gene expression in pathogenic Escherichia coli O157:H7 strain EDL933. BMC Genomics 10:349PubMedPubMedCentralCrossRefGoogle Scholar
  23. Dong T, Kirchhof MG, Schellhorn HE (2008) RpoS regulation of gene expression during exponential growth of Escherichia coli K12. Mol Genet Genomics 279:267–277PubMedCrossRefGoogle Scholar
  24. Farewell A, Diez AA, DiRusso CC, Nystrom T (1996) Role of the Escherichia coli FadR regulator in stasis survival and growth phase-dependent expression of the uspA, fad, and fab genes. J Bacteriol 178:6443–6450PubMedPubMedCentralCrossRefGoogle Scholar
  25. Feigenbaum J, Schulz H (1975) Thiolases of Escherichia coli: purification and chain length specificities. J Bacteriol 122:407–411PubMedPubMedCentralGoogle Scholar
  26. Feng Y, Cronan JE (2010) Overlapping repressor binding sites result in additive regulation of Escherichia coli FadH by FadR and ArcA. J Bacteriol 192:4289–4299PubMedPubMedCentralCrossRefGoogle Scholar
  27. Feng Y, Cronan JE (2011) Complex binding of the FabR repressor of bacterial unsaturated fatty acid biosynthesis to its cognate promoters. Mol Microbiol 80:195–218PubMedPubMedCentralCrossRefGoogle Scholar
  28. Feng Y, Cronan JE (2012) Crosstalk of Escherichia coli FadR with global regulators in expression of fatty acid transport genes. PLoS One 7:e46275PubMedPubMedCentralCrossRefGoogle Scholar
  29. Fonseca P, de la Peña F, Prieto MA (2014) A role for the regulator PsrA in the polyhydroxyalkanoate metabolism of Pseudomonas putida KT2440. Int J Biol Macromol 71:14–20PubMedCrossRefGoogle Scholar
  30. Fujihashi M, Nakatani T, Hirooka K, Matsuoka H, Fujita Y, Miki K (2014) Structural characterization of a ligand-bound form of Bacillus subtilis FadR involved in the regulation of fatty acid degradation. Proteins 82:1301–1310PubMedCrossRefGoogle Scholar
  31. Fujita Y, Matsuoka H, Hirooka K (2007) Regulation of fatty acid metabolism in bacteria. Mol Microbiol 66:829–839PubMedCrossRefGoogle Scholar
  32. Görke B, Stülke J (2008) Carbon catabolite repression in bacteria: many ways to make the most out of nutrients. Nat Rev Microbiol 6:613–624PubMedCrossRefGoogle Scholar
  33. Gui L, Sunnarborg A, Laporte DC (1996) Regulated expression of a repressor protein: FadR activates iclR. J Bacteriol 178:4704–4709PubMedPubMedCentralCrossRefGoogle Scholar
  34. Haydon DJ, Guest JR (1991) A new family of bacterial regulatory proteins. FEMS Microbiol Lett 63:291–295PubMedCrossRefGoogle Scholar
  35. Heidelberg JF, Eisen JA, Nelson WC, Clayton RA, Gwinn ML, Dodson RJ, Haft DH, Hickey EK, Peterson JD, Umayam L, Gill SR, Nelson KE, Read TD, Tettelin H, Richardson D, Ermolaeva MD, Vamathevan J, Bass S, Qin H, Dragoi I, Sellers P, McDonald L, Utterback T, Fleishmann RD, Nierman WC, White O, Salzberg SL, Smith HO, Colwell RR, Mekalanos JJ, Venter JC, Fraser CM (2000) DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae. Nature 406:477–483PubMedCrossRefGoogle Scholar
  36. Heidelberg JF, Paulsen IT, Nelson KE, Gaidos EJ, Nelson WC, Read TD, Eisen JA, Seshadri R, Ward N, Methe B, Clayton RA, Meyer T, Tsapin A, Scott J, Beanan M, Brinkac L, Daugherty S, DeBoy RT, Dodson RJ, Durkin AS, Haft DH, Kolonay JF, Madupu R, Peterson JD, Umayam LA, White O, Wolf AM, Vamathevan J, Weidman J, Impraim M, Lee K, Berry K, Lee C, Mueller J, Khouri H, Gill J, Utterback TR, McDonald LA, Feldblyum TV, Smith HO, Venter JC, Nealson KH, Fraser CM (2002) Genome sequence of the dissimilatory metal ion-reducing bacterium Shewanella oneidensis. Nat Biotechnol 20:1118–1123PubMedCrossRefPubMedCentralGoogle Scholar
  37. Hengge-Aronis R (2002) Signal transduction and regulatory mechanisms involved in control of the sigma(S) (RpoS) subunit of RNA polymerase. Microbiol Mol Biol Rev 66:373–395PubMedPubMedCentralCrossRefGoogle Scholar
  38. Henry MF, Cronan EJ (1991) Escherichia coli transcription factor that both activates fatty acid synthesis and represses fatty acid degradation. J Mol Biol 222:843–849PubMedCrossRefPubMedCentralGoogle Scholar
  39. Higashitani A, Nishimura Y, Hara H, Aiba H, Mizuno T, Horiuchi K (1993) Osmoregulation of the fatty acid receptor gene fadL in Escherichia coli. Mol Gen Genet 240:339–347PubMedGoogle Scholar
  40. Hubbard P, Liang X, Schulz H, Kim J-JP (2003) The crystal structure and reaction mechanism of Escherichia coli 2,4-dienoyl-CoA reductase. J Biol Chem 278:37553–37560PubMedCrossRefGoogle Scholar
  41. Iram SH, Cronan JE (2005) Unexpected functional diversity among FadR fatty acid transcriptional regulatory proteins. J Biol Chem 280:32148–32156PubMedCrossRefGoogle Scholar
  42. Ishige K, Nagasawa S, Tokishita S, Mizuno T (1994) A novel device of bacterial signal transducers. EMBO J 13:5195–5202PubMedPubMedCentralCrossRefGoogle Scholar
  43. Iuchi S, Lin EC (1988) arcA (dye), a global regulatory gene in Escherichia coli mediating repression of enzymes in aerobic pathways. Proc Natl Acad Sci USA 85:1888–1892PubMedCrossRefGoogle Scholar
  44. Iuchi S, Lin EC (1991) Adaptation of Escherichia coli to respiratory conditions: regulation of gene expression. Cell 66:5–7PubMedCrossRefGoogle Scholar
  45. Iuchi S, Lin ECC (1992) Purification and phosphorylation of the Arc regulatory components of Escherichia coli. J Bacteriol 174:5617–5623PubMedPubMedCentralCrossRefGoogle Scholar
  46. Jenkins LS, Nunn WD (1987a) Genetic and molecular characterization of the genes involved in short-chain fatty acid degradation in Escherichia coli: The ato system. J Bacteriol 169:42–52PubMedPubMedCentralCrossRefGoogle Scholar
  47. Jenkins LS, Nunn WD (1987b) Regulation of the ato operon by the atoC gene in Escherichia coli. J Bacteriol 169:2096–2102PubMedPubMedCentralCrossRefGoogle Scholar
  48. Kang Y, Nguyen DT, Son MS, Hoang TT (2008) The Pseudomonas aeruginosa PsrA responds to long-chain fatty acid signals to regulate the fadBA5B-oxidation operon. Microbiology 154:1584–1598PubMedCrossRefGoogle Scholar
  49. Kazakov AE, Rodionov DA, Alm E, Arkin AP, Dubchak I, Gelfand MS (2009) Comparative genomics of regulation of fatty acid and branched-chain amino acid utilization in proteobacteria. J Bacteriol 191:52–64PubMedCrossRefGoogle Scholar
  50. Klein K, Steinberg R, Fiethen B, Overath P (1971) Fatty acid degradation in Escherichia coli. Eur J Biochem 19:442–450PubMedCrossRefPubMedCentralGoogle Scholar
  51. Kremling A, Geiselmann J, Ropers D, de Jong H (2015) Understanding carbon catabolite repression in Escherichia coli using quantitative models. Trends Microbiol 23:99–109PubMedCrossRefGoogle Scholar
  52. Kriel A, Bittner AN, Kim SH, Liu K, Tehranchi AK, Zou WY, Rendon S, Chen R, Tu BP, Wang JD (2012) Direct regulation of GTP homeostasis by (p)ppGpp: a critical component of viability and stress resistance. Mol Cell 48:231–241PubMedPubMedCentralCrossRefGoogle Scholar
  53. Li SJ, Cronan JE (1993) Growth rate regulation of Escherichia coli acetyl coenzyme A carboxylase, which catalyzed the first committed step of lipid biosynthesis. J Bacteriol 175:332–340PubMedPubMedCentralCrossRefGoogle Scholar
  54. Lioliou EE, Mimitou EP, Grigoroudis AI et al (2005) Phosphorylation activity of the response regulator of the two-component signal transduction system AtoS-AtoC in E. coli. Biochim Biophys Acta 1725:257–268PubMedCrossRefPubMedCentralGoogle Scholar
  55. Malpica R, Franco B, Rodriguez C, Kwon O, Georgellis D (2004) Identification of a quinone-sensitive redox switch in the ArcB sensor kinase. Proc Natl Acad Sci USA 101:13318–13323PubMedCrossRefGoogle Scholar
  56. Matsuoka H, Hirooka K, Fujita Y (2007) Organization and function of the YsiA regulon of Bacillus subtilis involved in fatty acid degradation. J Biol Chem 282:5180–5194PubMedCrossRefGoogle Scholar
  57. Morgan-Kiss RM, Cronan JE (2004) The Escherichia coli fadK (ydiD) gene encodes an anerobically regulated short chain acyl-CoA synthetase. J Biol Chem 279:37324–37333PubMedCrossRefPubMedCentralGoogle Scholar
  58. My L, Rekoske B, Lemke JJ, Viala JP, Gourse RL, Bouveret E (2013) Transcription of the Escherichia coli fatty acid synthesis operon fabHDG is directly activated by FadR and inhibited by ppGpp. J Bacteriol 195:3784–3795PubMedPubMedCentralCrossRefGoogle Scholar
  59. My L, Ghandour Achkar N, Viala JP, Bouveret E (2015) Reassessment of the genetic regulation of fatty acid synthesis in Escherichia coli: global positive control by the dual functional regulator FadR. J Bacteriol 197:1862–1872PubMedPubMedCentralCrossRefGoogle Scholar
  60. Nunn WD, Simons RW (1978) Transport of long-chain fatty acids by Escherichia coli: mapping and characterization of mutants in the fadL gene. Proc Natl Acad Sci 75:3377–3381PubMedCrossRefGoogle Scholar
  61. Nunn WD, Giffin K, Clark D, Cronan JE Jr (1983) Role for fadR in unsaturated fatty acid biosynthesis in Escherichia coli. J Bacteriol 154:554–560PubMedPubMedCentralGoogle Scholar
  62. Overath P, Pauli G (1969) Fatty acid degradation in Escherichia coli. Eur J Biochem 7:559–574PubMedCrossRefGoogle Scholar
  63. Pauli G, Overath P (1972) ato operon: a highly inducible system for acetoacetate and butyrate degradation in Escherichia coli. Eur J Biochem 29:553–562PubMedCrossRefPubMedCentralGoogle Scholar
  64. Pech-Canul A, Nogales J, Miranda-Molina A, Laura Álvarez L, Geiger O, José Soto M, López-Lara IM (2011) FadD is required for utilization of endogenous fatty acids released from membrane lipids. J Bacteriol 193:6295–6304PubMedPubMedCentralCrossRefGoogle Scholar
  65. Podkovyrov SM, Larson TJ (1996) Identification of promoter and stringent regulation of transcription of the fabH, fabD and fabG genes encoding fatty acid biosynthetic enzymes of Escherichia coli. Nucl Acids Res 24:1747–1752PubMedCrossRefGoogle Scholar
  66. Raetz CRH (1993) Bacterial endotoxins: extraordinary lipids that activate eucaryotic signal transduction. J. Bacteriol 175:5745–5753PubMedPubMedCentralCrossRefGoogle Scholar
  67. Raman N, DiRusso CC (1995) Analysis of acyl coenzyme A binding to the transcription factor FadR and identification of amino acid residues in the carboxyl terminus required for ligand binding. J Biol Chem 270:1092–1097PubMedCrossRefGoogle Scholar
  68. Raman N, Black PN, Dirusso CC (1997) Characterization of the fatty acid-responsive transcription factor FadR. Biochemical and genetic analyses of the native conformation and functional domains. J Biol Chem 272:30645–30650PubMedCrossRefGoogle Scholar
  69. Rodionov DA, Novichkov PS, Stavrovskaya ED, Rodionova IA, Li X, Kazanov MD, Ravcheev DA, Gerasimova AV, Kazakov AE, Kovaleva GY, Permina EA, Laikova ON, Overbeek R, Romine MF, Fredrickson JK, Arkin AP, Dubchak I, Osterman AL, Gelfand MS (2011) Comparative genomic reconstruction of transcriptional networks controlling central metabolism in the Shewanella genus. BMC Genomics 12 Suppl 1:S3PubMedCrossRefGoogle Scholar
  70. Rojo F (2010) Carbon catabolite repression in Pseudomonas: optimizing metabolic versatility and interactions with the environment. FEMS Microbiol Rev 34:658–684PubMedCrossRefGoogle Scholar
  71. Schweizer E, Hofmann J (2004) Microbial type I fatty acid synthases (FAS): major players in a network of cellular FAS systems. Microbiol Mol Biol Rev 68:501–517PubMedPubMedCentralCrossRefGoogle Scholar
  72. Shingler V (2010) Signal sensory systems that impact σ54-dependent transcription. FEMS Microbiol Rev 35:425–440PubMedCrossRefGoogle Scholar
  73. Sunnarborg A, Klumpp D, Chung T, LaPorte DC (1990) Regulation of the glyoxylate bypass operon: cloning and characterization of iclR. J Bacteriol 172:2642–2649PubMedPubMedCentralCrossRefGoogle Scholar
  74. van Aalten DMF, DiRusso CC, Knudsen J, Wierenga RK (2000) Crystal structure of FadR, a fatty acid-responsive transcription factor with a novel acyl coenzyme A-binding fold. EMBO J 19:5167–5177PubMedPubMedCentralCrossRefGoogle Scholar
  75. van Aalten DMF, DiRusso CC, Knudsen J (2001) The structural basis of acyl coenzyme A-dependent regulation of the transcription factor FadR. EMBO J 20:2041–2050PubMedPubMedCentralCrossRefGoogle Scholar
  76. Wang F, Xiao X, Ou HY, Gai Y, Wang F (2009) Role and regulation of fatty acid biosynthesis in the response of Shewanella piezotolerans WP3 to different temperatures and pressures. J Bacteriol 191:2574–2584PubMedPubMedCentralCrossRefGoogle Scholar
  77. Weeks G, Shapiro M, Burns RO, Wakil SJ (1969) Control of fatty acid metabolism. I. Induction of the enzymes of fatty acid oxidation in Escherichia coli. J Bacteriol 97:827–836PubMedPubMedCentralGoogle Scholar
  78. Weimar JD, DiRusso CC, Delio R, Black PN (2002) Functional role of fatty acyl-coenzyme A synthetase in the transmembrane movement and activation of exogenous long-chain fatty acids: amino acid residues within the ATP/AMP signature motif of Escherichia coli FadD are required for enzyme activity and fatty acid transport. J Biol Chem 277:29369–29376PubMedCrossRefGoogle Scholar
  79. Xu Y, Heath RJ, Li Z, Rock CO, White SW (2001) The FadR·DNA complex. Transcriptional control of fatty acid metabolism in Escherichia coli. J Biol Chem 276:17373–17379PubMedCrossRefGoogle Scholar
  80. Yang SY, Li JM, He XY, Cosloy SD, Schulz H (1988) Evidence that the fadB gene of the fadAB operon of Escherichia coli encodes 3-hydroxyacyl-coenzyme A (CoA) epimerase, delta 3-cis-delta 2-trans-enoyl-CoA isomerase, and enoyl-CoA hydratase in addition to 3-hydroxyacyl-CoA dehydrogenase. J Bacteriol 170:2543–2548PubMedPubMedCentralCrossRefGoogle Scholar
  81. Yuan Y, Sachdeva M, Leeds JA, Meredith TC (2012) Fatty acid biosynthesis in Pseudomonas aeruginosa is initiated by the FabY class of β-ketoacyl acyl carrier protein synthases. J Bacteriol 194:5171–5184PubMedPubMedCentralCrossRefGoogle Scholar
  82. Zhang F, Ouelleta M, Battha TS, Adams PD, Petzolda CJ, Mukhopadhyaya A, Keasling JD (2012) Enhancing fatty acid production by the expression of the regulatory transcription factor FadR. Metabolic Engineering 14:653–660PubMedCrossRefGoogle Scholar
  83. Zhang H, Zheng B, Gao R, Feng Y (2015) Binding of Shewanella FadR to the fabA fatty acid biosynthetic gene: implications for contraction of the fad regulon. Protein Cell 6:667–679PubMedPubMedCentralCrossRefGoogle Scholar
  84. Zheng D, Constantinidou C, Hobman JL, Minchin SD (2004) Identification of the CRP regulon using in vitro and in vivo transcriptional profiling. Nucleic Acids Res 32:5874–5893PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Lorena Jimenez-Diaz
    • 1
    Email author
  • Antonio Caballero
    • 1
    • 2
  • Ana Segura
    • 1
    • 3
  1. 1.Abengoa ResearchSevillaSpain
  2. 2.BacmineTres CantosSpain
  3. 3.Department of Environmental ProtectionConsejo Superior de Investigaciones Científicas, Estación Experimental del ZaidínGranadaSpain

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