Components and Key Regulatory Steps of Lipid Biosynthesis in Actinomycetes

  • Gabriela Gago
  • Ana Arabolaza
  • Lautaro Diacovich
  • Hugo GramajoEmail author
Living reference work entry
Part of the Handbook of Hydrocarbon and Lipid Microbiology book series (HHLM)


The biochemical steps in fatty acid synthesis are highly conserved in bacteria and in most organisms. However, the data provided by the massive genomic sequencing revealed a surprising amount of diversity in the genes, enzymes, and genetic organization of the components responsible for bacterial lipid synthesis, with these differences being even more striking in the order Actinomycetales. Fatty acid biosynthesis is energetically very expensive for the cell; therefore, adjusting the rate of fatty acid synthesis, in order to maintain membrane lipid homeostasis, is a key factor for bacterial survival. Bacteria have evolved sophisticated and diverse mechanisms to finely control the expression of the genes responsible for the synthesis of fatty acids and, in some cases, also by regulating the activity of the pacemaker enzymes. In this chapter we summarize the main components of fatty acid biosynthesis and their regulation in different genera of actinomycetes, highlighting the main differences found between them and also with other bacteria. The main focus has been put into the acyl-CoA carboxylases, the fatty acid synthases, and on the regulatory elements that control these pathways.



This work was supported by NIH (1R01AI095183-01), ANPCyT PICT-2012-0168, PICT 2015-2022 and PID-2013-0042 to HG, PICT 2015-0796 to GG, PICT 2013-1981 to AA, and PICT 2014-1454 to LD.


  1. Alvarez HM (2016) Triacylglycerol and wax ester-accumulating machinery in prokaryotes. Biochimie 120:28–39PubMedCrossRefGoogle Scholar
  2. Alvarez HM, Steinbüchel A (2002) Triacylglycerols in prokaryotic microorganisms. Appl Microbiol Biotechnol 60:367–376PubMedCrossRefPubMedCentralGoogle Scholar
  3. Arabolaza A, D’Angelo M, Comba S, Gramajo H (2010) FasR, a novel class of transcriptional regulator, governs the activation of fatty acid biosynthesis genes in Streptomyces coelicolor. Mol Microbiol 78:47–63PubMedGoogle Scholar
  4. Astarie-Dequeker C, Le Guyader L, Malaga W et al (2009) Phthiocerol dimycocerosates of M. tuberculosis participate in macrophage invasion by inducing changes in the organization of plasma membrane lipids. PLoS Pathog 5(2):e1000289PubMedPubMedCentralCrossRefGoogle Scholar
  5. Athappilly FK, Hendrickson WA (1995) Structure of the biotinyl domain of acetyl-coenzyme A carboxylase determined by MAD phasing. Structure 3:1407–1419PubMedCrossRefGoogle Scholar
  6. Banerjee A, Dubnau E, Quemard A et al (1994) inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science 263:227–230PubMedCrossRefGoogle Scholar
  7. Bazet Lyonnet B, Diacovich L, Gago G et al (2017) Functional reconstitution of the Mycobacterium tuberculosis long-chain acyl-CoA carboxylase from multiple acyl-CoA subunits. FEBS J 284:1110–1125PubMedCrossRefPubMedCentralGoogle Scholar
  8. Bendt AK, Burkovski A, Schaffer S et al (2003) Towards a phosphoproteome map of Corynebacterium glutamicum. Proteomics 3:1637–1646PubMedCrossRefGoogle Scholar
  9. Bhatt A, Fujiwara N, Bhatt K et al (2007) Deletion of kasB in Mycobacterium tuberculosis causes loss of acid-fastness and subclinical latent tuberculosis in immunocompetent mice. Proc Natl Acad Sci USA 104:5157–5162PubMedCrossRefGoogle Scholar
  10. Biswas RK, Dutta D, Tripathi A et al (2013) Identification and characterization of Rv0494: a fatty acid-responsive protein of the GntR/FadR family from Mycobacterium tuberculosis. Microbiology 159:913–923PubMedCrossRefGoogle Scholar
  11. Blanchard CZ, Chapman-Smith A, Wallace JC, Waldrop GL (1999) The biotin domain peptide from the biotin carboxyl carrier protein of Escherichia coli acetyl-CoA carboxylase causes a marked increase in the catalytic efficiency of biotin carboxylase and carboxyltransferase relative to free biotin. J Biol Chem 274:31767–31769PubMedCrossRefGoogle Scholar
  12. Boehringer D, Ban N, Leibundgut M (2013) 7.5-Å cryo-EM structure of the mycobacterial fatty acid synthase. J Mol Biol 425:841–849PubMedCrossRefGoogle Scholar
  13. Borgaro JG, Chang A, Machutta CA et al (2011) Substrate recognition by β-ketoacyl-ACP synthases. Biochemistry 50:10678–10686PubMedPubMedCentralCrossRefGoogle Scholar
  14. Brennan PJ (2003) Structure, function, and biogenesis of the cell wall of Mycobacterium tuberculosis. Tuberculosis 83:91–97PubMedCrossRefGoogle Scholar
  15. Brignole EJ, Smith S, Asturias FJ (2009) Conformational flexibility of metazoan fatty acid synthase enables catalysis. Nat Struct Mol Biol 16:190–197PubMedPubMedCentralCrossRefGoogle Scholar
  16. Brown AK, Sridharan S, Kremer L et al (2005) Probing the mechanism of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III mt FabH: factors influencing catalysis and substrate specificity. J Biol Chem 280:32539–32547PubMedCrossRefGoogle Scholar
  17. Cabruja M, Mondino S, Tsai YT et al (2017) A conditional mutant of the fatty acid synthase unveils unexpected cross talks in mycobacterial lipid metabolism. Open Biol 7(2):160277PubMedPubMedCentralCrossRefGoogle Scholar
  18. Camacho LR, Ensergueix D, Perez E et al (1999) Identification of a virulence gene cluster of Mycobacterium tuberculosis by signature-tagged transposon mutagenesis. Mol Microbiol 34:257–267PubMedCrossRefGoogle Scholar
  19. Chiaradia L, Lefebvre C, Parra J et al (2017) Dissecting the mycobacterial cell envelope and defining the composition of the native mycomembrane. Sci Rep 7:12807PubMedPubMedCentralCrossRefGoogle Scholar
  20. Chopra T, Gokhale RS (2009) Polyketide versatility in the biosynthesis of complex mycobacterial cell wall lipids. Methods Enzymol 459:259–94.Google Scholar
  21. Ciccarelli L, Connell SR, Enderle M et al (2013) Structure and conformational variability of the Mycobacterium tuberculosis fatty acid synthase multienzyme complex. Structure 21:1251PubMedCrossRefGoogle Scholar
  22. Comba S, Menendez-Bravo S, Arabolaza A, Gramajo H (2013) Identification and physiological characterization of phosphatidic acid phosphatase enzymes involved in triacylglycerol biosynthesis in Streptomyces coelicolor. Microb Cell Fact 12:9PubMedPubMedCentralCrossRefGoogle Scholar
  23. Cox JS, Chen B, McNeil M, Jacobs WR Jr (1999) Complex lipid determines tissue-specific replication of Mycobacterium tuberculosis in mice. Nature 402:79–83PubMedCrossRefGoogle Scholar
  24. Cronan JE (2001) The biotinyl domain of Escherichia coli acetyl-CoA carboxylase. J Biol Chem 276:37355–37364PubMedCrossRefGoogle Scholar
  25. Cronan JE Jr, Subrahmanyam S (1998) FadR, transcriptional co-ordination of metabolic expediency. Mol Microbiol 29:937–943PubMedCrossRefGoogle Scholar
  26. Cronan JE Jr, Waldrop GL (2002) Multi-subunit acetyl-CoA carboxylases. Prog Lipid Res 41:407–435PubMedCrossRefGoogle Scholar
  27. Daffe M (2008) The global architecture of the mycobacterial cell envelope. In: Daffé M, Reyrat JM (eds) The mycobacterial cell envelope. ASM Press, Washington, DC, pp 3–11CrossRefGoogle Scholar
  28. Daffe M, Draper P (1998) The envelope layers of mycobacteria with reference to their pathogenicity. Adv Microb Physiol 39:131–203PubMedCrossRefGoogle Scholar
  29. Daffé M, Crick DC, Jackson M (2014) Genetics of capsular polysaccharides and cell envelope (glyco)lipids. Microbiol Spectr 2:MGM2-0021-2013PubMedCrossRefGoogle Scholar
  30. Daniel J, Oh TJ, Lee CM, Kolattukudy PE (2007) AccD6, a member of the Fas II locus, is a functional carboxyltransferase subunit of the acyl-coenzyme A carboxylase in Mycobacterium tuberculosis. J Bacteriol 189:911–917PubMedCrossRefPubMedCentralGoogle Scholar
  31. Das A, Khosla C (2009) Biosynthesis of aromatic polyketides in bacteria. Acc Chem Res 42:631–639PubMedPubMedCentralCrossRefGoogle Scholar
  32. Davis MS (2001) Inhibition of Escherichia coli acetyl coenzyme A carboxylase by acyl-acyl carrier protein. J Bacteriol 183:1499–1503PubMedPubMedCentralCrossRefGoogle Scholar
  33. Diacovich L, Peiru S, Kurth D et al (2002) Kinetic and structural analysis of a new group of acyl-CoA carboxylases found in Streptomyces coelicolor A3(2). J Biol Chem 277:31228–31236PubMedCrossRefPubMedCentralGoogle Scholar
  34. DiRusso CC, Nystrom T (1998) The fats of Escherichia coli during infancy and old age: regulation by global regulators, alarmones and lipid intermediates. Mol Microbiol 27:1–8PubMedCrossRefPubMedCentralGoogle Scholar
  35. Florova G, Kazanina G, Reynolds KA (2002) Enzymes involved in fatty acid and polyketide biosynthesis in Streptomyces glaucescens : role of FabH and FabD and their acyl carrier protein specificity. Biochemistry 41:10462–10471PubMedCrossRefPubMedCentralGoogle Scholar
  36. Fujita Y, Matsuoka H, Hirooka K (2007) Regulation of fatty acid metabolism in bacteria. Mol Microbiol 66:829–839PubMedCrossRefGoogle Scholar
  37. Gago G, Kurth D, Diacovich L et al (2006) Biochemical and structural characterization of an essential acyl coenzyme A carboxylase from Mycobacterium tuberculosis. J Bacteriol 188:477–486PubMedPubMedCentralCrossRefGoogle Scholar
  38. Gago G, Diacovich L, Arabolaza A et al (2011) Fatty acid biosynthesis in actinomycetes. FEMS Microbiol Rev 35:475–497PubMedPubMedCentralCrossRefGoogle Scholar
  39. Gande R, Gibson KJC, Brown AK et al (2004) Acyl-CoA carboxylases (accD2 and accD3), together with a unique polyketide synthase (Cg-pks), are key to mycolic acid biosynthesis in Corynebacterianeae such as Corynebacterium glutamicum and Mycobacterium tuberculosis. J Biol Chem 279:44847–44857PubMedCrossRefPubMedCentralGoogle Scholar
  40. Gande R, Dover LG, Krumbach K et al (2007) The two carboxylases of Corynebacterium glutamicum essential for fatty acid and mycolic acid synthesis. J Bacteriol 189:5257–5264PubMedPubMedCentralCrossRefGoogle Scholar
  41. Gao LY, Laval F, Lawson EH et al (2003) Requirement for kasB in Mycobacterium mycolic acid biosynthesis, cell wall impermeability and intracellular survival: implications for therapy. Mol Microbiol 49:1547–1563PubMedCrossRefPubMedCentralGoogle Scholar
  42. Gastambide O, Lederer E (1960) Biosynthesis of corynomycolic acid from 2 molecules of palmitic acid. Biochem Z 333:285–295Google Scholar
  43. Gebhardt H, Meniche X, Tropis M et al (2007) The key role of the mycolic acid content in the functionality of the cell wall permeability barrier in Corynebacterineae. Microbiology 153:1424–1434PubMedCrossRefPubMedCentralGoogle Scholar
  44. Gipson P, Mills DJ, Wouts R et al (2010) Direct structural insight into the substrate-shuttling mechanism of yeast fatty acid synthase by electron cryomicroscopy. Proc Natl Acad Sci USA 107:9164–9169PubMedCrossRefPubMedCentralGoogle Scholar
  45. Grininger M (2014) Perspectives on the evolution, assembly and conformational dynamics of fatty acid synthase type I (FAS I) systems. Curr Opin Struct Biol 25:49–56PubMedCrossRefPubMedCentralGoogle Scholar
  46. Haase FC, Henrikson KP, Treble DH, Allen SHG (1982) The subunit structure and function of the propionyl coenzyme A carboxylase of Mycobacterium smegmatis. J Biol Chem 257:11994–11999PubMedPubMedCentralGoogle Scholar
  47. Hernandez MA, Comba S, Arabolaza A et al (2015) Overexpression of a phosphatidic acid phosphatase type 2 leads to an increase in triacylglycerol production in oleaginous Rhodococcus strains. Appl Microbiol Biotechnol 99:2191–2207PubMedCrossRefPubMedCentralGoogle Scholar
  48. Hernandez M, Lara J, Gago G et al (2017) The pleiotropic transcriptional regulator NlpR contributes to the modulation of nitrogen metabolism, lipogenesis and triacylglycerol accumulation in oleaginous rhodococci. Mol Microbiol 103:366–385PubMedCrossRefGoogle Scholar
  49. Hoffmann C, Leis A, Niederweis M et al (2008) Disclosure of the mycobacterial outer membrane: cryo-electron tomography and vitreous sections reveal the lipid bilayer structure. Proc Natl Acad Sci U S A 105:3963–3967PubMedPubMedCentralCrossRefGoogle Scholar
  50. Hoischen C, Gura K, Luge C, Gumpert J (1997) Lipid and fatty acid composition of cytoplasmic membranes from Streptomyces hygroscopicus and its stable protoplast-type L form. J Bacteriol 179:3430–3436PubMedPubMedCentralCrossRefGoogle Scholar
  51. Hunaiti AR, Kolattukudy PE (1982) Isolation and characterization of an acyl-coenzyme A carboxylase from an erythromycin-producing Streptomyces erythreus. Arch Biochem Biophys 216:362–371PubMedCrossRefPubMedCentralGoogle Scholar
  52. Irzik K, van Ooyen J, Gätgens J et al (2014) Acyl-CoA sensing by FasR to adjust fatty acid synthesis in Corynebacterium glutamicum. J Biotechnol 192:96–101PubMedCrossRefGoogle Scholar
  53. Jamet S, Quentin Y, Coudray C et al (2015) Evolution of mycolic acid biosynthesis genes and their regulation during starvation in Mycobacterium tuberculosis. J Bacteriol 197:3797–3811PubMedPubMedCentralCrossRefGoogle Scholar
  54. Kalinowski J, Bathe B, Bartels D et al (2003) The complete Corynebacterium glutamicum ATCC 13032 genome sequence and its impact on the production of l-aspartate-derived amino acids and vitamins. J Biotechnol 104:5–25PubMedCrossRefGoogle Scholar
  55. Kaneda T (1991) Iso- and anteiso-fatty acids in bacteria: biosynthesis, function, and taxonomic significance. Microbiol Rev 55:288–302PubMedPubMedCentralGoogle Scholar
  56. Khan S, Nagarajan SN, Parikh A et al (2010) Phosphorylation of enoyl-acyl carrier protein reductase InhA impacts mycobacterial growth and survival. J Biol Chem 285:37860–37871PubMedPubMedCentralCrossRefGoogle Scholar
  57. Kikuchi S, Rainwater DL, Kolattukudy PE (1992) Purification and characterization of an unusually large fatty acid synthase from Mycobacterium tuberculosis var. bovis BCG. Arch Biochem Biophys 295:318–326PubMedCrossRefPubMedCentralGoogle Scholar
  58. Kurth DG, Gago GM, de la Iglesia A et al (2009) Accase 6 is the essential acetyl-CoA carboxylase involved in fatty acid and mycolic acid biosynthesis in mycobacteria. Microbiology 155:2664–2675PubMedPubMedCentralCrossRefGoogle Scholar
  59. Lane MD, Moss J, Polakis SE (1974) Acetyl coenzyme A carboxylase. Curr Top Cell Regul 8:139–195PubMedCrossRefGoogle Scholar
  60. Lanéelle MA, Tropis M, Daffé M (2013) Current knowledge on mycolic acids in Corynebacterium glutamicum and their relevance for biotechnological processes. Appl Microbiol Biotechnol 97:9923–9930PubMedCrossRefPubMedCentralGoogle Scholar
  61. Leibundgut M, Jenni S, Frick C, Ban N (2007) Structural basis for substrate delivery by acyl carrier protein in the yeast fatty acid synthase. Science 316:288–290PubMedCrossRefGoogle Scholar
  62. Leibundgut M, Maier T, Jenni S, Ban N (2008) The multienzyme architecture of eukaryotic fatty acid synthases. Curr Opin Struct Biol 18:714–725PubMedCrossRefGoogle Scholar
  63. Lin TW, Melgar MM, Kurth D et al (2006) Structure-based inhibitor design of AccD5, an essential acyl-CoA carboxylase carboxyltransferase domain of Mycobacterium tuberculosis. Proc Natl Acad Sci USA 103:3072–3077PubMedCrossRefPubMedCentralGoogle Scholar
  64. Lomakin IB, Xiong Y, Steitz TA (2007) The crystal structure of yeast fatty acid synthase, a cellular machine with eight active sites working together. Cell 129:319–332PubMedCrossRefPubMedCentralGoogle Scholar
  65. Maier T, Leibundgut M, Ban N (2008) The crystal structure of a mammalian fatty acid synthase. Science 321:1315–1323PubMedCrossRefGoogle Scholar
  66. Manteca A, Alvarez R, Salazar N et al (2008) Mycelium differentiation and antibiotic production in submerged cultures of Streptomyces coelicolor. Appl Environ Microbiol 74:3877–3886PubMedPubMedCentralCrossRefGoogle Scholar
  67. Marrakchi H, Ducasse S, Labesse G et al (2002) MabA (FabG1), a Mycobacterium tuberculosis protein involved in the long-chain fatty acid elongation system FAS-II. Microbiology 148:951–960PubMedCrossRefGoogle Scholar
  68. Meniche X, Otten R, Siegrist MS et al (2014) Subpolar addition of new cell wall is directed by DivIVA in mycobacteria. Proc Natl Acad Sci USA 111:E3243–E3251PubMedCrossRefGoogle Scholar
  69. Mo S, Sydor PK, Corre C et al (2008) Elucidation of the Streptomyces coelicolor pathway to 2-undecylpyrrole, a key intermediate in undecylprodiginine and streptorubin B biosynthesis. Chem Biol 15:137–148PubMedCrossRefGoogle Scholar
  70. Molle V, Kremer L (2010) Division and cell envelope regulation by Ser/Thr phosphorylation: Mycobacterium shows the way. Mol Microbiol 75:1064–1077PubMedCrossRefGoogle Scholar
  71. Molle V, Brown AK, Besra GS et al (2006) The condensing activities of the Mycobacterium tuberculosis type II fatty acid synthase are differentially regulated by phosphorylation. J Biol Chem 281:30094–30103PubMedCrossRefGoogle Scholar
  72. Mondino S, Gago G, Gramajo H (2013) Transcriptional regulation of fatty acid biosynthesis in mycobacteria. Mol Microbiol 89:372–387PubMedPubMedCentralCrossRefGoogle Scholar
  73. Munday MR (2002) Regulation of mammalian acetyl-CoA carboxylase. Biochem Soc Trans 30:1059–1064PubMedCrossRefGoogle Scholar
  74. Nickel J, Irzik K, Van Ooyen J, Eggeling L (2010) The TetR-type transcriptional regulator FasR of Corynebacterium glutamicum controls genes of lipid synthesis during growth on acetate. Mol Microbiol 78:253–265PubMedGoogle Scholar
  75. Oh TJ, Daniel J, Kim HJ et al (2006) Identification and characterization of Rv3281 as a novel subunit of a biotin-dependent acyl-CoA carboxylase in Mycobacterium tuberculosis H37Rv. J Biol Chem 281:3899–3908PubMedCrossRefGoogle Scholar
  76. Pawelczyk J, Brzostek A, Kremer L et al (2011) Accd6, a key carboxyltransferase essential for mycolic acid synthesis in Mycobacterium tuberculosis, is dispensable in a nonpathogenic strain. J Bacteriol 193:6960–6972PubMedPubMedCentralCrossRefGoogle Scholar
  77. Polakis SE, Guchhait RB, Lane MD (1973) Stringent control of fatty acid synthesis in Escherichia. J Biol Chem 248:7957–7967PubMedGoogle Scholar
  78. Portevin D, De Sousa-D’Auria C, Houssin C et al (2004) A polyketide synthase catalyzes the last condensation step of mycolic acid biosynthesis in mycobacteria and related organisms. Proc Natl Acad Sci USA 101:314–319PubMedCrossRefGoogle Scholar
  79. Portevin D, Auria DS, Montrozier H et al (2005) The Acyl-AMP ligase FadD32 and AccD4-containing acyl-CoA carboxylase are required for the synthesis of mycolic acids and essential for mycobacterial growth. J Biol Chem 280:8862–8874PubMedCrossRefPubMedCentralGoogle Scholar
  80. Puech V, Chami M, Lemassu A et al (2001) Structure of the cell envelope of corynebacteria: importance of the non-covalently bound lipids in the formation of the cell wall permeability barrier and fracture plane. Microbiology 147:1365–1382PubMedCrossRefGoogle Scholar
  81. Quémard A (2016) New insights into the compound biosynthesis and transport in mycobacteria. Trends Microbiol 24:725–738PubMedCrossRefGoogle Scholar
  82. Quemard A, Sacchettini C, Dessen A et al (1995) Enzymatic characterization of the target for isoniazid in Mycobacterium tuberculosis. Biochemistry 34:8235–8241PubMedCrossRefGoogle Scholar
  83. Radmacher E, Alderwick LJ, Besra GS et al (2005) Two functional FAS-I type fatty acid synthases in Corynebacterium glutamicum. Microbiology 151:2421–2427PubMedCrossRefGoogle Scholar
  84. Rangan V, Smith S (2003) Fatty acid synthesis in eukaryotes. In: Vance D, Vance J (eds) Biochemistry of lipids, lipoproteins and membranes. Elsevier, Amsterdam, pp 151–179Google Scholar
  85. Revill WP, Bibb MJ, Hopwood D (1995) Purification of a malonyltransferase from Streptomyces coelicolor A3(2) and analysis of its genetic determinant. J Bacteriol 177:3946–3952PubMedPubMedCentralCrossRefGoogle Scholar
  86. Revill WP, Bibb MJ, Hopwood D (1996) Relationships between fatty acid and polyketide synthases from Streptomyces coelicolor A3(2): characterization of the fatty acid synthase acyl carrier protein. J Bacteriol 178:5660–5667PubMedPubMedCentralCrossRefGoogle Scholar
  87. Richard-Greenblatt M, Av-Gay Y (2017) Epigenetic phosphorylation control of Mycobacterium tuberculosis infection and persistence. Microbiol Spectr 5(2):TBTB2-0005-2015CrossRefGoogle Scholar
  88. Rock CO, Jackowski S (2002) Forty years of bacterial fatty acid synthesis. Biochem Biophys Res Commun 292:1155–1166PubMedCrossRefGoogle Scholar
  89. Rottig A, Steinbuchel A (2013) Acyltransferases in bacteria. Microbiol Mol Biol Rev 77:277–321PubMedPubMedCentralCrossRefGoogle Scholar
  90. Sacco E, Covarrubias AS, O’Hare HM et al (2007) The missing piece of the type II fatty acid synthase system from Mycobacterium tuberculosis. Proc Natl Acad Sci USA 104:14628–14633PubMedCrossRefGoogle Scholar
  91. Salzman V, Mondino S, Sala C et al (2010) Transcriptional regulation of lipid homeostasis in mycobacteria. Mol Microbiol 78:64–77PubMedGoogle Scholar
  92. Sassetti CM, Boyd DH, Rubin EJ (2003) Genes required for mycobacterial growth defined by high density mutagenesis. Mol Microbiol 48:77–84PubMedCrossRefGoogle Scholar
  93. Scarsdale JN, Kazanina G, He X et al (2001) Crystal structure of the Mycobacterium tuberculosis beta ketoacyl-acyl carrier protein synthase III. J Biol Chem 276:20516–20522PubMedCrossRefGoogle Scholar
  94. Schaeffer ML, Agnihotri G, Volker C et al (2001) Purification and biochemical characterization of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthases KasA and KasB. J Biol Chem 276:47029–47037PubMedCrossRefGoogle Scholar
  95. 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 4:663–672PubMedCrossRefGoogle Scholar
  96. Schujman GE, Guerin M, Buschiazzo A et al (2006) Structural basis of lipid biosynthesis regulation in Gram-positive bacteria. EMBO J 25:4074–4083PubMedPubMedCentralCrossRefGoogle Scholar
  97. 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
  98. Singh R, Reynolds KA (2015) Characterization of FabG and FabI of the Streptomyces coelicolor dissociated fatty acid synthase. Chembiochem 16:631–640PubMedCrossRefGoogle Scholar
  99. Singh R, Mo S, Florova G, Reynolds KA (2012) Streptomyces coelicolor RedP and FabH enzymes, initiating undecylprodiginine and fatty acid biosynthesis, exhibit distinct acyl-CoA and malonyl-acyl carrier protein substrate specificities. FEMS Microbiol Lett 328:32–38PubMedCrossRefGoogle Scholar
  100. Slama N, Leiba J, Eynard N et al (2011) Negative regulation by Ser/Thr phosphorylation of HadAB and HadBC dehydratases from Mycobacterium tuberculosis type II fatty acid synthase system. Biochem Biophys Res Commun 412:401–406PubMedCrossRefGoogle Scholar
  101. Slayden RA, Barry CE III (2002) The role of KasA and KasB in the biosynthesis of meromycolic acids and isoniazid resistance in Mycobacterium tuberculosis. Tuberculosis 82:149–160PubMedCrossRefGoogle Scholar
  102. Sutcliffe IC (1997) Macroamphiphilic cell envelope components of Rhodococcus equi and closely related bacteria. Vet Microbiol 56:287–299PubMedCrossRefGoogle Scholar
  103. Takayama K, Wang C, Besra GS (2005) Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis. Clin Microbiol Rev 18:81–101PubMedPubMedCentralCrossRefGoogle Scholar
  104. Tauch A, Kaiser O, Hain T et al (2005) Complete genome sequence and analysis of the multiresistant nosocomial pathogen Corynebacterium jeikeium K411, a lipid-requiring bacterium of the human skin flora. J Bacteriol 187:4671–4682PubMedPubMedCentralCrossRefGoogle Scholar
  105. Tauch A, Trost E, Tilker A et al (2008) The lifestyle of Corynebacterium urealyticum derived from its complete genome sequence established by pyrosequencing. J Biotechnol 136:11–21PubMedCrossRefGoogle Scholar
  106. Tong L (2013) Structure and function of biotin-dependent carboxylases. Cell Mol Life Sci 70:863–891PubMedCrossRefGoogle Scholar
  107. Tran TH, Hsiao Y-S, Jo J et al (2015) Structure and function of a single-chain, multi-domain long-chain acyl-CoA carboxylase. Nature 518:120–124PubMedCrossRefGoogle Scholar
  108. Tsai YT, Salzman V, Cabruja M et al (2017) Role of long chain acyl-CoAs in the regulation of mycolic acid biosynthesis in mycobacteria. Open Biol 7:170087PubMedPubMedCentralCrossRefGoogle Scholar
  109. Veyron-Churlet R, Molle V, Taylor RC et al (2009) The Mycobacterium tuberculosis β-ketoacyl-acyl carrier protein synthase III activity is inhibited by phosphorylation on a single threonine residue. J Biol Chem 284:6414–6424PubMedPubMedCentralCrossRefGoogle Scholar
  110. Veyron-Churlet R, Zanella-Cléon I, Cohen-Gonsaud M et al (2010) Phosphorylation of the Mycobacterium tuberculosis β-ketoacyl-acyl carrier protein reductase MabA regulates mycolic acid biosynthesis. J Biol Chem 285:12714–12725PubMedPubMedCentralCrossRefGoogle Scholar
  111. Vilchèze C, Molle V, Carrère-Kremer S et al (2014) Phosphorylation of KasB regulates virulence and acid-fastness in Mycobacterium tuberculosis. PLoS Pathog 10(5):e1004115PubMedPubMedCentralCrossRefGoogle Scholar
  112. Wakil SJ, Stoops JK, Joshi VC (1983) Fatty acid synthesis and its regulation. Annu Rev Biochem 52:537–579PubMedCrossRefGoogle Scholar
  113. Waldrop GL, Rayment I, Holden HM (1994) Three-dimensional structure of the biotin carboxylase subunit of acetyl-CoA carboxylase. Biochemistry 33:10249–10256PubMedCrossRefGoogle Scholar
  114. White SW, Zheng J, Zhang YM, Rock (2005) The structural biology of type II fatty acid biosynthesis. Annu Rev Biochem 74:791–831PubMedCrossRefGoogle Scholar
  115. Xu WX, Zhang L, Mai JT et al (2014) The Wag31 protein interacts with AccA3 and coordinates cell wall lipid permeability and lipophilic drug resistance in Mycobacterium smegmatis. Biochem Biophys Res Commun 448:255–260PubMedCrossRefGoogle Scholar
  116. Xu Z, Wang M, Ye B-C (2017) TetR family transcriptional regulator PccD negatively controls propionyl coenzyme A assimilation in Saccharopolyspora erythraea. J Bacteriol 199:1–12CrossRefGoogle Scholar
  117. Yousuf S, Angara R, Vindal V, Ranjan A (2015) Rv0494 is a starvation-inducible, auto-regulatory FadR-like regulator from Mycobacterium tuberculosis. Microbiology 161:463–476PubMedCrossRefPubMedCentralGoogle Scholar
  118. Zhang Y-M, Rock CO (2008) Membrane lipid homeostasis in bacteria. Nat Rev Microbiol 6:222–233PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Gabriela Gago
    • 1
  • Ana Arabolaza
    • 1
  • Lautaro Diacovich
    • 1
  • Hugo Gramajo
    • 2
    Email author
  1. 1.Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET), Facultad de Ciencias Bioquímicas y FarmacéuticasUniversidad Nacional de RosarioRosarioArgentina
  2. 2.Department of Microbiology, Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET), Facultad de Ciencias Bioquímicas y FarmacéuticasUniversidad Nacional de RosarioRosarioArgentina

Personalised recommendations