Advertisement

Applied Microbiology and Biotechnology

, Volume 102, Issue 15, pp 6333–6341 | Cite as

Acyl-coenzyme A:(holo-acyl carrier protein) transacylase enzymes as templates for engineering

  • Aaron M. Marcella
  • Adam W. Barb
Mini-Review

Abstract

This review will cover the structure, enzymology, and related aspects that are important for structure-based engineering of the transacylase enzymes from fatty acid biosynthesis and polyketide synthesis. Furthermore, this review will focus on in vitro characteristics and not cover engineering of the upstream or downstream reactions or strategies to manipulate metabolic flux in vivo. The malonyl-coenzyme A(CoA)-holo-acyl-carrier protein (holo-ACP) transacylase (FabD) from Escherichia coli serves as a model for this enzyme with thorough descriptions of structure, enzyme mechanism, and effects of mutation on substrate binding presented in the literature. Here, we discuss multiple practical and theoretical considerations regarding engineering transacylase enzymes to accept non-cognate substrates and form novel acyl-ACPs for downstream reactions.

Keywords

Acyl-coenzyme A:(holo-acyl carrier protein) Transacylase enzymes Escherichia coli FabD 

Notes

Funding

This study was funded by the National Science Foundation (EEC-0813570).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. Alberts AW, Goldman P, Vagelos PR (1963) The condensation reaction of fatty acid synthesis. I. Separation and properties of the enzymes. J Biol Chem 238:557–565PubMedGoogle Scholar
  2. Alberts AW, Majerus PW, Talamo B, Vagelos PR (1964) Acyl-carrier protein. II. Intermediary reactions of fatty acid synthesis. Biochemistry 3:1563–1571CrossRefPubMedGoogle Scholar
  3. Aparicio JF, Caffrey P, Marsden AF, Staunton J, Leadlay PF (1994) Limited proteolysis and active-site studies of the first multienzyme component of the erythromycin-producing polyketide synthase. J Biol Chem 269(11):8524–8528PubMedGoogle Scholar
  4. Bar-Even A, Noor E, Savir Y, Liebermeister W, Davidi D, Tawfik DS, Milo R (2011) The moderately efficient enzyme: evolutionary and physicochemical trends shaping enzyme parameters. Biochemistry 50(21):4402–4410.  https://doi.org/10.1021/bi2002289 CrossRefPubMedGoogle Scholar
  5. Barajas JF, Blake-Hedges JM, Bailey CB, Curran S, Keasling JD (2017) Engineered polyketides: synergy between protein and host level engineering. Synth Syst Biotechnol 2(3):147–166.  https://doi.org/10.1016/j.synbio.2017.08.005 CrossRefPubMedPubMedCentralGoogle Scholar
  6. Beld J, Lee DJ, Burkart MD (2015) Fatty acid biosynthesis revisited: structure elucidation and metabolic engineering. Mol BioSyst 11(1):38–59.  https://doi.org/10.1039/c4mb00443d CrossRefPubMedGoogle Scholar
  7. Bergler H, Wallner P, Ebeling A, Leitinger B, Fuchsbichler S, Aschauer H, Kollenz G, Hogenauer G, Turnowsky F (1994) Protein EnvM is the NADH-dependent enoyl-ACP reductase (FabI) of Escherichia coli. J Biol Chem 269(8):5493–5496PubMedGoogle Scholar
  8. Borgaro JG, Chang A, Machutta CA, Zhang X, Tonge PJ (2011) Substrate recognition by beta-ketoacyl-ACP synthases. Biochemistry 50(49):10678–10686.  https://doi.org/10.1021/bi201199x CrossRefPubMedPubMedCentralGoogle Scholar
  9. Broussard TC, Price AE, Laborde SM, Waldrop GL (2013) Complex formation and regulation of Escherichia coli acetyl-CoA carboxylase. Biochemistry 52(19):3346–3357.  https://doi.org/10.1021/bi4000707 CrossRefPubMedGoogle Scholar
  10. Brown A, Affleck V, Kroon J, Slabas A (2009) Proof of function of a putative 3-hydroxyacyl-acyl carrier protein dehydratase from higher plants by mass spectrometry of product formation. FEBS Lett 583(2):363–368.  https://doi.org/10.1016/j.febslet.2008.12.022 CrossRefPubMedGoogle Scholar
  11. Campbell JW, Cronan JE Jr (2001) Bacterial fatty acid biosynthesis: targets for antibacterial drug discovery. Annu Rev Microbiol 55:305–332.  https://doi.org/10.1146/annurev.micro.55.1.305 CrossRefPubMedGoogle Scholar
  12. Chan M, Himes RH, Akagi JM (1971) Fatty acid composition of thermophilic, mesophilic, and psychrophilic clostridia. J Bacteriol 106(3):876–881PubMedPubMedCentralGoogle Scholar
  13. Chan YA, Podevels AM, Kevany BM, Thomas MG (2009) Biosynthesis of polyketide synthase extender units. Nat Prod Rep 26(1):90–114CrossRefPubMedPubMedCentralGoogle Scholar
  14. Chan YA, Thomas MG (2009) Formation and characterization of acyl carrier protein-linked polyketide synthase extender units. Methods Enzymol 459:143–163.  https://doi.org/10.1016/S0076-6879(09)04607-2 CrossRefPubMedPubMedCentralGoogle Scholar
  15. Chen L, Lee J, Chen WN (2016) The use of metabolic engineering to produce fatty acid-derived biofuel and chemicals in Saccharomyces cerevisiae: a review. AIMS Bioengineering 3(4):468–492CrossRefGoogle Scholar
  16. Crick FH (1952) Is alpha-keratin a coiled coil? Nature 170(4334):882–883CrossRefPubMedGoogle Scholar
  17. Crick FH (1953) The packing of a-helices: simple coiled-coils. Acta Cryst 6:689–697CrossRefGoogle Scholar
  18. Cronan JE, Thomas J (2009) Bacterial fatty acid synthesis and its relationships with polyketide synthetic pathways. Methods Enzymol 459:395–433.  https://doi.org/10.1016/S0076-6879(09)04617-5 CrossRefPubMedPubMedCentralGoogle Scholar
  19. Davies C, Heath RJ, White SW, Rock CO (2000) The 1.8 A crystal structure and active-site architecture of beta-ketoacyl-acyl carrier protein synthase III (FabH) from Escherichia coli. Structure 8(2):185–195CrossRefPubMedGoogle Scholar
  20. Davila-Martinez Y, Ramos-Vega AL, Contreras-Martinez S, Encarnacion S, Geiger O, Lopez-Lara IM (2010) SMc01553 is the sixth acyl carrier protein in Sinorhizobium meliloti 1021. Microbiology 156(Pt 1):230–239.  https://doi.org/10.1099/mic.0.033480-0 CrossRefPubMedGoogle Scholar
  21. Donadio S, Staver MJ, McAlpine JB, Swanson SJ, Katz L (1991) Modular organization of genes required for complex polyketide biosynthesis. Science 252(5006):675–679CrossRefPubMedGoogle Scholar
  22. Dreier J, Li Q, Khosla C (2001) Malonyl-CoA:ACP transacylase from Streptomyces coelicolor has two alternative catalytically active nucleophiles. Biochemistry 40(41):12407–12411CrossRefPubMedGoogle Scholar
  23. Dunn BJ, Khosla C (2013) Engineering the acyltransferase substrate specificity of assembly line polyketide synthases. J R Soc Interface 10(85):20130297.  https://doi.org/10.1098/rsif.2013.0297 CrossRefPubMedPubMedCentralGoogle Scholar
  24. Dunn BJ, Watts KR, Robbins T, Cane DE, Khosla C (2014) Comparative analysis of the substrate specificity of trans- versus cis-acyltransferases of assembly line polyketide synthases. Biochemistry 53(23):3796–3806.  https://doi.org/10.1021/bi5004316 CrossRefPubMedPubMedCentralGoogle Scholar
  25. El Boulifi N, Aracil J, Martinez M (2010) Lipase-catalyzed synthesis of isosorbide monoricinoleate: process optimization by response surface methodology. Bioresour Technol 101(22):8520–8525.  https://doi.org/10.1016/j.biortech.2010.06.094 CrossRefPubMedGoogle Scholar
  26. Elovson J, Vagelos PR (1968) Acyl carrier protein. X. Acyl carrier protein synthetase. J Biol Chem 243(13):3603–3611PubMedGoogle Scholar
  27. 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(33):10462–10471CrossRefPubMedGoogle Scholar
  28. Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003) Experimental determination and system level analysis of essential genes in Escherichia coli MG1655. J Bacteriol 185(19):5673–5684CrossRefPubMedPubMedCentralGoogle Scholar
  29. Goldman P, Alberts AW, Vagelos PR (1963a) The condensation reaction of fatty acid biosynthesis. II. Requirement of the enzymes of the condensation reaction for fatty acid synthesis. J Biol Chem 238:1255–1261PubMedGoogle Scholar
  30. Goldman P, Alberts AW, Vagelos PR (1963b) The condensation reaction of fatty acid Synthesis. III. Identification of the protein-bound product of the reaction and its conversion to long chain fatty acids. J Biol Chem 238:3579–3583PubMedGoogle Scholar
  31. Gronenberg LS, Marcheschi RJ, Liao JC (2013) Next generation biofuel engineering in prokaryotes. Curr Opin Chem Biol 17(3):462–471.  https://doi.org/10.1016/j.cbpa.2013.03.037 CrossRefPubMedPubMedCentralGoogle Scholar
  32. Guchhait RB, Polakis SE, Dimroth P, Stoll E, Moss J, Lane MD (1974) Acetyl coenzyme A carboxylase system of Escherichia coli. Purification and properties of the biotin carboxylase, carboxyltransferase, and carboxyl carrier protein components. J Biol Chem 249(20):6633–6645PubMedGoogle Scholar
  33. Harwood JL (1996) Recent advances in the biosynthesis of plant fatty acids. Biochim Biophys Acta 1301(1–2):7–56CrossRefPubMedGoogle Scholar
  34. Haydock SF, Aparicio JF, Molnar I, Schwecke T, Khaw LE, Konig A, Marsden AF, Galloway IS, Staunton J, Leadlay PF (1995) Divergent sequence motifs correlated with the substrate specificity of (methyl)malonyl-CoA:acyl carrier protein transacylase domains in modular polyketide synthases. FEBS Lett 374(2):246–248CrossRefPubMedGoogle Scholar
  35. Heath RJ, Rock CO (1996a) Inhibition of beta-ketoacyl-acyl carrier protein synthase III (FabH) by acyl-acyl carrier protein in Escherichia coli. J Biol Chem 271(18):10996–11000CrossRefPubMedGoogle Scholar
  36. Heath RJ, Rock CO (1996b) Regulation of fatty acid elongation and initiation by acyl-acyl carrier protein in Escherichia coli. J Biol Chem 271(4):1833–1836CrossRefPubMedGoogle Scholar
  37. Hiltunen JK, Schonauer MS, Autio KJ, Mittelmeier TM, Kastaniotis AJ, Dieckmann CL (2009) Mitochondrial fatty acid synthesis type II: more than just fatty acids. J Biol Chem 284(14):9011–9015.  https://doi.org/10.1074/jbc.R800068200 CrossRefPubMedPubMedCentralGoogle Scholar
  38. Jackowski S, Rock CO (1987) Acetoacetyl-acyl carrier protein synthase, a potential regulator of fatty acid biosynthesis in bacteria. J Biol Chem 262(16):7927–7931PubMedGoogle Scholar
  39. Janssen HJ, Steinbuchel A (2014) Fatty acid synthesis in Escherichia coli and its applications towards the production of fatty acid based biofuels. Biotechnol Biofuels 7(1):7.  https://doi.org/10.1186/1754-6834-7-7 CrossRefPubMedPubMedCentralGoogle Scholar
  40. Joshi VC (1972) Mechanism of malonyl-coenzyme A-acyl-carrier protein transacylase. Biochem J 128(1):43P–44PCrossRefPubMedPubMedCentralGoogle Scholar
  41. Joshi VC, Wakil SJ (1971) Studies on the mechanism of fatty acid synthesis. XXVI. Purification and properties of malonyl-coenzyme A—acyl carrier protein transacylase of Escherichia coli. Arch Biochem Biophys 143(2):493–505CrossRefPubMedGoogle Scholar
  42. Keatinge-Clay AT, Shelat AA, Savage DF, Tsai SC, Miercke LJ, O'Connell JD 3rd, Khosla C, Stroud RM (2003) Catalysis, specificity, and ACP docking site of Streptomyces coelicolor malonyl-CoA:ACP transacylase. Structure 11(2):147–154CrossRefPubMedGoogle Scholar
  43. Khosla C (2009) Structures and mechanisms of polyketide synthases. J Org Chem 74(17):6416–6420.  https://doi.org/10.1021/jo9012089 CrossRefPubMedGoogle Scholar
  44. Kondo H, Shiratsuchi K, Yoshimoto T, Masuda T, Kitazono A, Tsuru D, Anai M, Sekiguchi M, Tanabe T (1991) Acetyl-CoA carboxylase from Escherichia coli: gene organization and nucleotide sequence of the biotin carboxylase subunit. Proc Natl Acad Sci U S A 88(21):9730–9733CrossRefPubMedPubMedCentralGoogle Scholar
  45. Kremer L, Nampoothiri KM, Lesjean S, Dover LG, Graham S, Betts J, Brennan PJ, Minnikin DE, Locht C, Besra GS (2001) Biochemical characterization of acyl carrier protein (AcpM) and malonyl-CoA:AcpM transacylase (mtFabD), two major components of Mycobacterium tuberculosis fatty acid synthase II. J Biol Chem 276(30):27967–27974.  https://doi.org/10.1074/jbc.M103687200 CrossRefPubMedGoogle Scholar
  46. Lambalot RH, Walsh CT (1995) Cloning, overproduction, and characterization of the Escherichia coli holo-acyl carrier protein synthase. J Biol Chem 270(42):24658–24661CrossRefPubMedGoogle Scholar
  47. Leibundgut M, Maier T, Jenni S, Ban N (2008) The multienzyme architecture of eukaryotic fatty acid synthases. Curr Opin Struct Biol 18(6):714–725.  https://doi.org/10.1016/j.sbi.2008.09.008 CrossRefPubMedGoogle Scholar
  48. Li Z, Huang Y, Ge J, Fan H, Zhou X, Li S, Bartlam M, Wang H, Rao Z (2007) The crystal structure of MCAT from Mycobacterium tuberculosis reveals three new catalytic models. J Mol Biol 371(4):1075–1083.  https://doi.org/10.1016/j.jmb.2007.06.004 CrossRefPubMedGoogle Scholar
  49. Lim YP, Go MK, Yew WS (2016) Exploiting the biosynthetic potential of type III polyketide synthases. Molecules 21(6).  https://doi.org/10.3390/molecules21060806
  50. 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(2):319–332.  https://doi.org/10.1016/j.cell.2007.03.013 CrossRefPubMedGoogle Scholar
  51. Lu X, Vora H, Khosla C (2008) Overproduction of free fatty acids in E. coli: implications for biodiesel production. Metab Eng 10(6):333–339.  https://doi.org/10.1016/j.ymben.2008.08.006 CrossRefPubMedGoogle Scholar
  52. Maier T, Leibundgut M, Ban N (2008) The crystal structure of a mammalian fatty acid synthase. Science 321(5894):1315–1322.  https://doi.org/10.1126/science.1161269 CrossRefPubMedGoogle Scholar
  53. Majerus PW, Alberts AW, Vagelos PR (1964) The acyl carrier protein of fatty acid synthesis: purification, physical properties, and substrate binding site. Proc Natl Acad Sci U S A 51:1231–1238CrossRefPubMedPubMedCentralGoogle Scholar
  54. Marcella AM, Barb AW (2016) A rapid fluorometric assay for the S-malonyltransacylase FabD and other sulfhydryl utilizing enzymes. J Biol Methods 3(4):53.  https://doi.org/10.14440/jbm.2016.144 CrossRefGoogle Scholar
  55. Marcella AM, Barb AW (2017) The R117A variant of the Escherichia coli transacylase FabD synthesizes novel acyl-(acyl carrier proteins). Appl Microbiol Biotechnol 101(23–24):8431–8441.  https://doi.org/10.1007/s00253-017-8586-9 CrossRefPubMedGoogle Scholar
  56. Marcella AM, Culbertson SJ, Shogren-Knaak MA, Barb AW (2017) Structure, high affinity, and negative cooperativity of the Escherichia coli holo-(acyl carrier protein):holo-(acyl carrier protein) synthase complex. J Mol Biol 429(23):3763–3775.  https://doi.org/10.1016/j.jmb.2017.10.015 CrossRefPubMedGoogle Scholar
  57. Marcella AM, Jing F, Barb AW (2015) Preparation of holo- and malonyl-[acyl-carrier-protein] in a manner suitable for analog development. Protein Expr Purif 115:39–45.  https://doi.org/10.1016/j.pep.2015.05.013 CrossRefPubMedGoogle Scholar
  58. McAllister KA, Peery RB, Zhao G (2006) Acyl carrier protein synthases from gram-negative, gram-positive, and atypical bacterial species: biochemical and structural properties and physiological implications. J Bacteriol 188(13):4737–4748.  https://doi.org/10.1128/JB.01917-05 CrossRefPubMedPubMedCentralGoogle Scholar
  59. Misra A, Surolia N, Surolia A (2009) Catalysis and mechanism of malonyl transferase activity in type II fatty acid biosynthesis acyl carrier proteins. Mol BioSyst 5(6):651–659.  https://doi.org/10.1039/b820420a CrossRefPubMedGoogle Scholar
  60. Molnos J, Gardiner R, Dale GE, Lange R (2003) A continuous coupled enzyme assay for bacterial malonyl-CoA:acyl carrier protein transacylase (FabD). Anal Biochem 319(1):171–176CrossRefPubMedGoogle Scholar
  61. Musiol EM, Hartner T, Kulik A, Moldenhauer J, Piel J, Wohlleben W, Weber T (2011) Supramolecular templating in kirromycin biosynthesis: the acyltransferase KirCII loads ethylmalonyl-CoA extender onto a specific ACP of the trans-AT PKS. Chem Biol 18(4):438–444.  https://doi.org/10.1016/j.chembiol.2011.02.007 CrossRefPubMedGoogle Scholar
  62. Nguyen T, Ishida K, Jenke-Kodama H, Dittmann E, Gurgui C, Hochmuth T, Taudien S, Platzer M, Hertweck C, Piel J (2008) Exploiting the mosaic structure of trans-acyltransferase polyketide synthases for natural product discovery and pathway dissection. Nat Biotechnol 26(2):225–233.  https://doi.org/10.1038/nbt1379 CrossRefPubMedGoogle Scholar
  63. Nikolau BJ, Perera MA, Brachova L, Shanks B (2008) Platform biochemicals for a biorenewable chemical industry. Plant J 54(4):536–545.  https://doi.org/10.1111/j.1365-313X.2008.03484.x CrossRefPubMedGoogle Scholar
  64. Oefner C, Schulz H, D'Arcy A, Dale GE (2006) Mapping the active site of Escherichia coli malonyl-CoA-acyl carrier protein transacylase (FabD) by protein crystallography. Acta Crystallogr D Biol Crystallogr 62(Pt 6):613–618.  https://doi.org/10.1107/S0907444906009474 CrossRefPubMedGoogle Scholar
  65. Orsavova J, Misurcova L, Ambrozova JV, Vicha R, Mlcek J (2015) Fatty acids composition of vegetable oils and its contribution to dietary energy intake and dependence of cardiovascular mortality on dietary intake of fatty acids. Int J Mol Sci 16(6):12871–12890.  https://doi.org/10.3390/ijms160612871 CrossRefPubMedPubMedCentralGoogle Scholar
  66. Parris KD, Lin L, Tam A, Mathew R, Hixon J, Stahl M, Fritz CC, Seehra J, Somers WS (2000) Crystal structures of substrate binding to Bacillus subtilis holo-(acyl carrier protein) synthase reveal a novel trimeric arrangement of molecules resulting in three active sites. Structure 8(8):883–895CrossRefPubMedGoogle Scholar
  67. Pech-Canul A, Nogales J, Miranda-Molina A, Alvarez L, Geiger O, Soto MJ, Lopez-Lara IM (2011) FadD is required for utilization of endogenous fatty acids released from membrane lipids. J Bacteriol 193(22):6295–6304.  https://doi.org/10.1128/JB.05450-11 CrossRefPubMedPubMedCentralGoogle Scholar
  68. Ploux O, Masamune S, Walsh CT (1988) The NADPH-linked acetoacetyl-CoA reductase from Zoogloea ramigera. Characterization and mechanistic studies of the cloned enzyme over-produced in Escherichia coli. Eur J Biochem 174(1):177–182CrossRefPubMedGoogle Scholar
  69. Ramos-Vega AL, Davila-Martinez Y, Sohlenkamp C, Contreras-Martinez S, Encarnacion S, Geiger O, Lopez-Lara IM (2009) SMb20651 is another acyl carrier protein from Sinorhizobium meliloti. Microbiology 155(Pt 1):257–267.  https://doi.org/10.1099/mic.0.022079-0 CrossRefPubMedGoogle Scholar
  70. Rangan VS, Smith S (1997) Alteration of the substrate specificity of the malonyl-CoA/acetyl-CoA:acyl carrier protein S-acyltransferase domain of the multifunctional fatty acid synthase by mutation of a single arginine residue. J Biol Chem 272(18):11975–11978CrossRefPubMedGoogle Scholar
  71. Reeves CD, Murli S, Ashley GW, Piagentini M, Hutchinson CR, McDaniel R (2001) Alteration of the substrate specificity of a modular polyketide synthase acyltransferase domain through site-specific mutations. Biochemistry 40(51):15464–15470CrossRefPubMedGoogle Scholar
  72. Reuter K, Mofid MR, Marahiel MA, Ficner R (1999) Crystal structure of the surfactin synthetase-activating enzyme sfp: a prototype of the 4′-phosphopantetheinyl transferase superfamily. EMBO J 18(23):6823–6831.  https://doi.org/10.1093/emboj/18.23.6823 CrossRefPubMedPubMedCentralGoogle Scholar
  73. Ridgway JB, Presta LG, Carter P (1996) ‘Knobs-into-holes’ engineering of antibody CH3 domains for heavy chain heterodimerization. Protein Eng 9(7):617–621CrossRefPubMedGoogle Scholar
  74. Ruch FE, Vagelos PR (1973a) Characterization of a malonyl-enzyme intermediate and identification of the malonyl binding site in malonyl coenzyme A-acyl carrier protein transacylase of Escherichia coli. J Biol Chem 248(23):8095–8106PubMedGoogle Scholar
  75. Ruch FE, Vagelos PR (1973b) The isolation and general properties of Escherichia coli malonyl coenzyme A-acyl carrier protein transacylase. J Biol Chem 248(23):8086–8094PubMedGoogle Scholar
  76. Serre L, Swenson L, Green R, Wei Y, Verwoert II, Verbree EC, Stuitje AR, Derewenda ZS (1994) Crystallization of the malonyl coenzyme A-acyl carrier protein transacylase from Escherichia coli. J Mol Biol 242(1):99–102.  https://doi.org/10.1006/jmbi.1994.1559 CrossRefPubMedGoogle Scholar
  77. Serre L, Verbree EC, Dauter Z, Stuitje AR, Derewenda ZS (1995) The Escherichia coli malonyl-CoA:acyl carrier protein transacylase at 1.5-A resolution. Crystal structure of a fatty acid synthase component. J Biol Chem 270(22):12961–12964CrossRefPubMedGoogle Scholar
  78. Sharma SK, Kapoor M, Ramya TN, Kumar S, Kumar G, Modak R, Sharma S, Surolia N, Surolia A (2003) Identification, characterization, and inhibition of Plasmodium falciparum beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ). J Biol Chem 278(46):45661–45671.  https://doi.org/10.1074/jbc.M304283200 CrossRefPubMedGoogle Scholar
  79. Shen B (2003) Polyketide biosynthesis beyond the type I, II and III polyketide synthase paradigms. Curr Opin Chem Biol 7(2):285–295CrossRefPubMedGoogle Scholar
  80. Sheppard AJ, Iverson JL, Weihrauch JL (1978) Fatty acids and glycerides, Composition of selected dietary fats, oils, margarines, and butter. Handb Lip Res 1:341–379Google Scholar
  81. Singh SP, Zhou XR, Liu Q, Stymne S, Green AG (2005) Metabolic engineering of new fatty acids in plants. Curr Opin Plant Biol 8(2):197–203.  https://doi.org/10.1016/j.pbi.2005.01.012 CrossRefPubMedGoogle Scholar
  82. Smith S, Witkowski A, Joshi AK (2003) Structural and functional organization of the animal fatty acid synthase. Prog Lipid Res 42(4):289–317CrossRefPubMedGoogle Scholar
  83. Staunton J, Weissman KJ (2001) Polyketide biosynthesis: a millennium review. Nat Prod Rep 18(4):380–416CrossRefPubMedGoogle Scholar
  84. Szafranska AE, Hitchman TS, Cox RJ, Crosby J, Simpson TJ (2002) Kinetic and mechanistic analysis of the malonyl CoA:ACP transacylase from Streptomyces coelicolor indicates a single catalytically competent serine nucleophile at the active site. Biochemistry 41(5):1421–1427CrossRefPubMedGoogle Scholar
  85. Tang X, Lee J, Chen WN (2015) Engineering the fatty acid metabolic pathway in Saccharomyces cerevisiae for advanced biofuel production. Metab Eng Comm 2:58–66CrossRefGoogle Scholar
  86. Tee TW, Chowdhury A, Maranas CD, Shanks JV (2014) Systems metabolic engineering design: fatty acid production as an emerging case study. Biotechnol Bioeng 111(5):849–857.  https://doi.org/10.1002/bit.25205 CrossRefPubMedPubMedCentralGoogle Scholar
  87. Toomey RE, Wakil SJ (1966) Studies on the mechanism of fatty acid synthesis XV. Preparation and general properties of beta-ketoacyl acyl carrier protein reductase fromi. Biochim Biophys Acta 116(2):189–197 doi:0005-2760(66)90001-4 [pii]CrossRefPubMedGoogle Scholar
  88. Tsay JT, Oh W, Larson TJ, Jackowski S, Rock CO (1992) Isolation and characterization of the beta-ketoacyl-acyl carrier protein synthase III gene (fabH) from Escherichia coli K-12. J Biol Chem 267(10):6807–6814PubMedGoogle Scholar
  89. Vick JE, Clomburg JM, Blankschien MD, Chou A, Kim S, Gonzalez R (2015) Escherichia coli enoyl-acyl carrier protein reductase (FabI) supports efficient operation of a functional reversal of beta-oxidation cycle. Appl Environ Microbiol 81(4):1406–1416.  https://doi.org/10.1128/AEM.03521-14 CrossRefPubMedPubMedCentralGoogle Scholar
  90. Wakil SJ, Stoops JK, Joshi VC (1983) Fatty acid synthesis and its regulation. Annu Rev Biochem 52:537–579.  https://doi.org/10.1146/annurev.bi.52.070183.002541 CrossRefPubMedGoogle Scholar
  91. White SW, Zheng J, Zhang YM, Rock (2005) The structural biology of type II fatty acid biosynthesis. Annu Rev Biochem 74:791–831.  https://doi.org/10.1146/annurev.biochem.74.082803.133524 CrossRefPubMedGoogle Scholar
  92. Zhou P, Florova G, Reynolds KA (1999) Polyketide synthase acyl carrier protein (ACP) as a substrate and a catalyst for malonyl ACP biosynthesis. Chem Biol 6(8):577–584.  https://doi.org/10.1016/S1074-5521(99)80090-8 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Roy J. Carver Department of Biochemistry, Biophysics and Molecular BiologyIowa State UniversityAmesUSA

Personalised recommendations