Journal of Applied Biological Chemistry

The Korean Society for Applied Biological Chemistry (한국응용생명화학회)
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Biosynthesis of Polyunsaturated Fatty Acids: Metabolic Engineering in Plants

고도불포화지방산 생합성: 식물에서의 대사공학적 응용

  • Kim, Sun-Hee (Functional Bio-Material Division, National Academy of Agricultural Science, RDA) ;
  • Kim, So-Yun (Functional Bio-Material Division, National Academy of Agricultural Science, RDA) ;
  • Kim, Jong-Bum (Functional Bio-Material Division, National Academy of Agricultural Science, RDA) ;
  • Roh, Kyung-Hee (Functional Bio-Material Division, National Academy of Agricultural Science, RDA) ;
  • Kim, Young-Mi (Functional Bio-Material Division, National Academy of Agricultural Science, RDA) ;
  • Park, Jong-Sug (Functional Bio-Material Division, National Academy of Agricultural Science, RDA)
  • 김순희 (농촌진흥청 국립농업과학원 기능성물질개발과) ;
  • 김소연 (농촌진흥청 국립농업과학원 기능성물질개발과) ;
  • 김종범 (농촌진흥청 국립농업과학원 기능성물질개발과) ;
  • 노경희 (농촌진흥청 국립농업과학원 기능성물질개발과) ;
  • 김영미 (농촌진흥청 국립농업과학원 기능성물질개발과) ;
  • 박종석 (농촌진흥청 국립농업과학원 기능성물질개발과)
  • Published : 2009.09.30
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Abstract

Polyunsaturated fatty acids (PUFA), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have significantly beneficial effects on health in relation to cardiovascular, immune, and inflammatory conditions and they are involved in determining the biophysical properties of membranes as well as being precursors for signaling molecules. PUFA biosynthesis is catalyzed by sequential desaturation and fatty acyl elongation reactions. This aerobic biosynthetic pathway was thought to be taxonomically conserved, but an alternative anaerobic pathway for the biosynthesis of PUFA is now known to contain analogous polyketide synthases (PKS). Certain fish oil can be a rich source of PUFA although processed marine oil is generally undesirable as food ingredients because of the associated objectionable flavors that are difficult and cost-prohibitive to remove. Oil-seed plants contain only the 18-carbon polyunsaturated fatty acid alpha-linolenic acid, which is not converted in the human body to EPA and DHA. It is now possible to engineer common oilseeds which can produce EPA and DHA and this has been the focus of a number of academic and industrial research groups. Recent advances and future prospects in the production of EPA and DHA in oilseed crops are discussed here.

Keywords

References

  1. Abbadi A, Domergue F, Bauer J, Napier JA, Welti R, Zahringer U, Cirpus P, and Heinz E (2004) Biosynthesis of very-long-chain polyunsaturated fatty acidsin transgenic oilseeds: constraints on their accumulation. Plant Cell 16, 2734-2748 https://doi.org/10.1105/tpc.104.026070
  2. Aitzetmuller K and Tsevegsuren N (1994) Occurrence of $\gamma$-linolenic acid in Ranunculaceae seed oils. J Plant Physiol 143, 538-543
  3. Allen EE and Bartlett DH (2002) Structure and regulation of the Omega-3 polyunsaturated fatty acid synthase genes from the deep-sea bacterium photobacterium profondum strain SS9. Microbiology 148, 1903-1913
  4. Beaudoin F, Gable K, Sayanova O, Dunn T, and Napier JA (2002) A Saccharomyces cerevisiae gene required for heterologous fatty acid elongase activity encodes a microsomal beta-ketoreductase. J BioI Chem 277, 11481-11488 https://doi.org/10.1074/jbc.M111441200
  5. Beaudoin F, Michaelson LV, Hey SJ, Lewis MJ, Shewry PR, Sayanova O, and Napier JA (2000) Heterologous reconstitution in yeast of the polyunsaturated fatty acid biosynthetic pathway. Proc Natl Acad Sci USA 97, 6421-6426 https://doi.org/10.1073/pnas.110140197
  6. Benatti P, Peluso G, Nicolai R, and Calvani M (2004) Polyunsaturated fatty acids: biochemical, nutritional and epigenetic properties. J Am Coll Nutr 23, 281-302
  7. Bloch K (1969) Enzymatic synthesis of monounsaturated fatty acids. Acc Chem Res 2, 193-202 https://doi.org/10.1021/ar50019a001
  8. Bloomfield DK and Bloch K (1960) Formation of $^{\circ}$,9-unsaturated fatty acids. J BioI Chem 235, 337-345
  9. Broker M, Bauml O, Gottig A, Ochs J, Bodenbenner M, and Amann E (1991) Expression of the human blood coagulation protein factor XIIIa in Saccharomyces cerevisiae: dependence of the expression levels from hostvector systems and medium conditions. Appl Microbiol Biotechnol 34, 756-764 https://doi.org/10.1007/BF00169346
  10. Browse J, McConn M, James D Jr, and Miquel M (1993) Mutants of Arabidopsis deficient in the synthesis of alpha-linolenate. Biochemical and genetic characterization of the endoplasmic reticulum linoleoyl desaturase. J BioI Chem 268, 16345-16351
  11. Cho HP, Nakamura M, and Clarke SD (1999) Cloning, expression, and fatty acid regulation of the human delta-5 desaturase. J BioI Chem 274, 37335-37339 https://doi.org/10.1074/jbc.274.52.37335
  12. Crawford MA, Costeloe K, Ghebremeskel K, Phylactos A, Skirvin L, and Stacey F (1997) Are deficits of arachidonic and docosahexaenoic acids responsible for the neural and vascular complications of preterm babies? Am J Clin Nutr 66, 1032S-1041S https://doi.org/10.1093/ajcn/66.4.1032S
  13. Damude HG and Kinney AJ (2008) Enhancing plant seed oils for human nutrition. Plant Physiol 147, 962-968 https://doi.org/10.1104/pp.108.121681
  14. Domergue F, Abbadi A, and Heinz E (2005) Relief for fish stocks: oceanic fatty acids in transgenic oilseeds. Trends Plant Sci 10, 112-116
  15. Domergue F, Abbadi A, Ott C, Zank TK, Zahringer U, and Heinz E (2003a) Acyl carriers used as substrates by the desaturases and elongases involved in very long-chain polyunsaturated fatty acids biosynthesis reconstituted in yeast. J BioI Chem 278, 35115-35126 https://doi.org/10.1074/jbc.M305990200
  16. Domergue F, Spiekermann P, Lerchl J, Beckmann C, Kilian O, Kroth PG, Boland W, Zahringer U, and Heinz E (2003b) New insight into Phaeodactylum tricormutum fatty acid metabolism: cloning and functional characterization of plastidial and microsomal $\Delta$12-fatty acid desaturases. Plant Physiol 131, 1648-1660 https://doi.org/10.1104/pp.102.018317
  17. Denic V and Weissman JS (2007) A molecular caliper mechanism for determining very long-chain fatty acid length. Cell 130, 663-677 https://doi.org/10.1016/j.cell.2007.06.031
  18. Fulco AJ (1974) Metabolic alteration of fatty acids. Annu Rev Biochem 43, 215-240 https://doi.org/10.1146/annurev.bi.43.070174.001243
  19. Girke T, Schmidt H, Zahringer U, Reski R, and Heinz E (1998) Identification of a novel D6-acyl-group desaturase by targeted gene disruption in Physcomitrella patens. Plant J 15, 39-48 https://doi.org/10.1046/j.1365-313X.1998.00178.x
  20. Graham lA, Larson T, and Napier JA (2007) Rational metabolic engineering of transgenic plants for biosynthesis of omega-3 polyunsaturates. Curr Opin Plant BioI 18, 142-147
  21. Han G, Gable K, Kohlwein SD, Beaudoin F, Napier JA, and Dunn TM (2002) The Saccharomyces cerevisiae YBRI59w gene encodes the 3-ketoreductase of the microsomal fatty acid elongase. J BioI Chem 277, 35440-35449 https://doi.org/10.1074/jbc.M205620200
  22. Hastings N, Agaba M, Tocher DR, Leaver MJ, and Dick JR, et al. (2001) A vertebrate fatty acid desaturase with delta 5 and delta 6 activities. Proc Natl Acad Sci USA 98, 14304-14309 https://doi.org/10.1073/pnas.251516598
  23. Heird WC and Lapillonne A (2005) The role of essential fatty acids in development. Annu Rev Nutr 25, 549-571 https://doi.org/10.1146/annurev.nutr.24.012003.132254
  24. Huang YS, Chaudhary S, Thurmond JM, Bobik EG, Jr, Yuan L, Chan GM, Kirchner SJ, Mukerji P, and Knutzon DS (1999) Cloning of $\Delta$12-and $\Delta$6-desaturases from Mortierella alpina and recombinant production of $\gamma$-linolenic acid in Saccharomyces cerevisiae. Lipids 34, 649-659 https://doi.org/10.1007/s11745-999-0410-8
  25. Iba K, Gibson S, Nishiuchi T, Fuse T, and Nishimura M, et al. (1993) A gene encoding a chloroplast omega-3 fatty acid desaturase complements alterations in fatty acid desaturation and chloroplast copy number of the fad7 mutant of Arabidopsis thaliana. J BioI Chem 268, 24099-24105
  26. Jakobsson A, Westerberg R, and lacobsson A (2006) Fatty acid elongases in mammals: their regulation and roles in metabolism. Prog Lipid Res 45, 237-249 https://doi.org/10.1016/j.plipres.2006.01.004
  27. James Jr DW, Lim E, Keller J, Plooy I, Ralston E, and Dooner HK (1995) Directed Tagging of the Arabidopsis FATTY ACID ELONGATION1 (FAE1) Gene with the Maize Transposon Activator. Plant Cell 7, 309-319 https://doi.org/10.1105/tpc.7.3.309
  28. Jenni S, Leibundgut M, Boehringer D, Frick C, Mikolasek B, and Ban N (2007) Structure of fungal fatty acid synthase and implications for iterative substrate shuttling. Science 316, 254-261 https://doi.org/10.1126/science.1138248
  29. Kinney AJ, Cahoon EB, Damude HG, Hitz WD, Kolar CW, Liu ZB. August 10, 2004. Production of very long chain polyunsaturated fatty acids in oilseed plants. International Patent Publication WO 2004071467
  30. Knutzon DS, Thurmond JM, Huang YS, Chaudhary S, Bobik EG, Jr, Chan GM, Kirchner SJ, and Mukerji P (1998) Identification of $\Delta$5-desaturase from Mortierella alpina by heterologous expression in Bakers' Yeast and Canola. J BioI Chem 273, 29360-29366 https://doi.org/10.1074/jbc.273.45.29360
  31. Kohlwein SD, Eder S, Oh CS, Martin CE, Gable K, Bacikova D, and Dunn T (2001) Tscl3p is required for fatty acid elongation and localizes to a novel structure at the nuclear-vacuolar interface in Saccharomyces cerevisiae. Mol Cell BioI 21, 109-125 https://doi.org/10.1128/MCB.21.1.109-125.2001
  32. Leonard AE, Pereira SL, Sprecher H, and Huang YS (2004) Elongation of long-chain fatty acids. Prog Lipid Res 43, 36-54 https://doi.org/10.1016/S0163-7827(03)00040-7
  33. Lomakin lB, Xiong Y, and Steitz TA (2007) The Crystal structure of yeast fatty acid synthase, a cellular machine with eight active sites working together. Cell 129, 319-332 https://doi.org/10.1016/j.cell.2007.03.013
  34. Marquardt A, Stohr H, White K, and Weber BH (2000) cDNA cloning, genomic structure, and chromosomal localization of three members of the human fatty acid desaturase family. Genomics 66, 175-183 https://doi.org/10.1006/geno.2000.6196
  35. Marszalek JR and Lodish JF (2005) Docosahexaenoic acid, fatty acid-interacting proteins, and neuronal function: breastmilk and fish are good for you. Annu Rev Cell Dev BioI 21, 633-657 https://doi.org/10.1146/annurev.cellbio.21.122303.120624
  36. Martinez-Rivas JM, Sperling P, Luhs W, and Heinz E (2001) Spatial and temporal regulation of three different microsomal oleate desaturase genes (FAD2) from normal-type and higholeic varieties of sunflower (Helianthus annuus L.). Mol Breeding 8, 159-168 https://doi.org/10.1023/A:1013324329322
  37. McConn M, Hugly S, Browse J, and Somerville C (1994) A mutation at the fad8 locus of Arabidopsis identifies a second chloroplast omega-3 desaturase. Plant Physiol 106, 1609-1614
  38. Metz JG, Flatt JH, Kuner JM. December 21, 2006. PUFA polyketide synthase systems and uses there of. International Patent Publication WO 2006135866
  39. Metz JG, Roessler P, Facciotti D, Levering C, Dittrich F, Lassner M, Valentine R, Lardizabal K, Domergue F, Yamada A, Knauf V, and Browse J (2001) Production of polyunsaturated fatty acids by polyketide synthases in both prokaryotes and eukaryotes. Science 293, 290-293 https://doi.org/10.1126/science.1059593
  40. Meyer A, Kirsch H, Domergue F, Abbadi A, Sperling P, Bauer J, Cirpus P, Zank TK, Moreau H, and Roscoe TJ (2004) Novel fatty acid elongases and their use for the reconstitution of docosahexaenoic acid biosynthesis. J Lipid Res 45, 1899-1909 https://doi.org/10.1194/jlr.M400181-JLR200
  41. Michaelson LV, Napier JA, Lewis M, Griffiths G, Lazarus CM, and Stobart AK (1998) Functional identification of a fatty acid $\Delta$5-desaturase gene from Caenorhabditis elegans. FEBS Lett 439, 215-218 https://doi.org/10.1016/S0014-5793(98)01385-4
  42. Moon YA, Shah NA, Mohapatra S, Warrington JA, and Horton JD (2001) Identification of a mammalian long chain fatty acyl elongase regulated by sterol regulatory element-binding proteins. J BioI Chem 276, 45358-45366 https://doi.org/10.1074/jbc.M108413200
  43. Napier JA (2002) Plumbing the depths of PUFA biosynthesis: a novel polyketide synthase-like pathway from marine organisms. Trends Plant Sci 7, 51-54 https://doi.org/10.1016/S1360-1385(01)02191-4
  44. Nichols DS, Nichols PD, and McMeekin TA (1993) Polyunsaturated fatty acids in Antarctic bacteria. Antarctic Sci 2, 149-160 https://doi.org/10.1017/S0954102093000215
  45. Nugteren DH (1965) The enzymic chain elongation of fatty acids by rat-liver microsomes. Biochim Biophys Acta 106, 280-290 https://doi.org/10.1016/0005-2760(65)90036-6
  46. Oh CS, Toke DA, Mandala S, and Martin CE (1997) ELO2 and ELO3, homologues of the Saccharomyces cerevisiae ELO1 gene, function in fatty acid elongation and are required for sphingolipid formation. J Bioi Chem 272, 17376-17384 https://doi.org/10.1074/jbc.272.28.17376
  47. Okayasu T, Nagao M, Ishibashi T, and Imai Y (1981) Purification and partial characterization of linoleoyl-CoA desaturase from rat liver microsomes. Arch Biochem Biophys 206, 21-28 https://doi.org/10.1016/0003-9861(81)90061-8
  48. Paul S, Gable K, Beaudoin F, Cahoon E, Jaworski J, Napier JA, and Dunn TM (2006) Members of the Arabidopsis FAE1-like 3-Ketoacyl-CoA synthase gene family substitute for the Elop proteins of Saccharomyces cerevisiae. J BioI Chem 281, 9018-9029 https://doi.org/10.1074/jbc.M507723200
  49. Pereira SL, Huang YS, Bobik EG, Kinney AJ, Stecca KL, Packer JC, and Mukerji P (2004a) A novel omega 3-fatty acid desaturase involved in the biosynthesis of eicosapentaenoic acid. Biochem J 378, 665-671 https://doi.org/10.1042/BJ20031319
  50. Pereira SL, Leonard AE, Huang YS, Chuang LT, and Mukerji P (2004b) Identification of two novel microalgal enzymes involved in the conversion of the omega3-fatty acid, eicosapentaenoic acid, into docosahexaenoic acid. Biochem J 384, 357-366 https://doi.org/10.1042/BJ20040970
  51. Qi B, Fraser T, Mugford S, Dobson G, Sayanova O, ButlerJ, Napier JA, Stobart AK, and Lazarus CM (2004) Production of very long chain polyunsaturated omega-3 and omega-6 fatty acids in plants. Nat Biotechnol 22, 739-745 https://doi.org/10.1038/nbt972
  52. Qiu X (2003) Biosynthesis of docosahexaenoic acid (DHA, 22:6-4, 7, 10, 13, 16, 19): two distinct pathways. Prostaglandins Leukot Essent Fatty Acids 68, 181-186 https://doi.org/10.1016/S0952-3278(02)00268-5
  53. Robert S, Singh S, Zhou X, Petrie J, Blackburn S, Mansour P, Nichols PD, Liu Q, and Green AG (2005) Metabolic engineering of Arabidopsis to produce nutritionally important DHA in seed oil. Funct Plant BioI 32, 473-479 https://doi.org/10.1071/FP05084
  54. Schroepfer GJ and Bloch K (1965) The stereospecific conversion of stearic acid to oleic acid. J Bioi Chem 240, 54-63
  55. Singh SP, Zhou XR, Liu Q, Stymne S, and Green AG (2005) Metabolic engineering of new fatty acids in plants. Curr Opin Plant Biol 8, 197-203 https://doi.org/10.1016/j.pbi.2005.01.012
  56. Sperling P, Lee M, Girke T, Zahringer U, Stymne S, and Heinz E (2000) A bifunctional delta-fatty acyl acetylenase/desaturase from the moss Ceratodon purpureus: a new member of the cytochrome b5 superfamily. Eur J Biochem 267, 3801-3811 https://doi.org/10.1046/j.1432-1327.2000.01418.x
  57. Sprecher H (1999) An update on the pathways of polyunsaturated fatty acid metabolism. Curr Opin Clin Nutr Metab Care 2, 135-138 https://doi.org/10.1097/00075197-199903000-00007
  58. Sprecher H, Luthria DL, Mohammed BS, and Baykousheva SP (1995) Reevaluation of the pathways for the biosynthesis of polyunsaturated fatty acids. J Lipid Res 36, 2471-2477
  59. Stillwell W and Wassail SR (2003) Docosahexaenoic acid:membrane properties of a unique fatty acid. Chem Phys Lipids 126, 1-27 https://doi.org/10.1016/S0009-3084(03)00101-4
  60. Strittmatter P, Spatz L, Corcoran M, Rogers MI, Setlow B, and Redline B (1974) Purification and properties of rat liver microsomal stearoyl coenzyme A desaturase. Proc Natl Acad Sci USA 71, 4565-4569 https://doi.org/10.1073/pnas.71.11.4565
  61. Takeyama H, Takeda D, Yazawa K, Yomada A, and Matsunaga T (1997) Expression of the eicosapentaeonic acid synthesis gene cluster from Shewanella sp. in a transgenic marine cyanobacterium Synechococcus sp. Microbiology 143, 2725-2731 https://doi.org/10.1099/00221287-143-8-2725
  62. Theiede M and Strittmatter P (1985) The induction and characterization of rat liver stearoyl-CoA desaturase mRNA. J BioI Chem 260, 14459-14463
  63. Truksa M, Wu G, Vrinten P, and Qiu X (2006) Metabolic engineering of plants to produce very long·chain polyunsaturated fatty acids. Transgenic Res 15, 131-137 https://doi.org/10.1007/s11248-005-6069-8
  64. Valentine RC and Valentine DL (2004) Omega-3 fatty acids in cellular membranes: a unified concept. Prog Lipid Res 43, 383-402 https://doi.org/10.1016/j.plipres.2004.05.004
  65. Wallis JG and Browse J (1999) The Delta8-desaturase of Euglena gracilis: an alternate pathway for synthesis of 20-carbon polyunsaturated fatty acids. Arch Biochem Biophys 365, 307-316 https://doi.org/10.1006/abbi.1999.1167
  66. Wallis JG, Watts JL, and Browse J (2002) Polyunsaturated fatty acid synthesis: what will they think of next? Trends Biochem Sci 27, 467-473 https://doi.org/10.1016/S0968-0004(02)02168-0
  67. Westerberg R, Mansson JE, Golozoubova V, Shabalina IG, Backlund EC, Tvrdik P, Retterstol K, Capecchi MR, and Jacobsson A (2006) ELOVL3 is an important component for early onset of lipid recruitment in brown adipose tissue. J Biol Chem 281, 4958-4968 https://doi.org/10.1074/jbc.M511588200
  68. Wu G Truksa M, Datla N, Vrinten P, Bauer J, and Zank T et al. (2005) Stepwise engineering to produce high yields of very long-chain polyunsaturated fatty acids in plants. Nat Biotechnol 23, 1013-1017 https://doi.org/10.1038/nbt1107
  69. Yazawa K (1996) Production of eicosapentaenoic acid by marine bacteria. Lipids 31, 297S-300S https://doi.org/10.1007/BF02637095
  70. Zolfaghari R,Cifelli CJ, Banta MD, and Ross AC (2001) Fatty acid delta (5)-desaturase mRNA is regulated by dietary vitamin A and exogenous rctinoic acid in liver of adult rats. Arch Biochem Biophys 391, 8-15 https://doi.org/10.1006/abbi.2001.2361

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