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Applied Microbiology and Biotechnology

, Volume 102, Issue 7, pp 3027–3035 | Cite as

Biosynthesis of nervonic acid and perspectives for its production by microalgae and other microorganisms

  • Yong Fan
  • Hui-Min Meng
  • Guang-Rong Hu
  • Fu-Li Li
Mini-Review

Abstract

Nervonic acid (NA) is a major very long-chain monounsaturated fatty acid found in the white matter of mammalian brains, which plays a critical role in the treatment of psychotic disorders and neurological development. In the nature, NA has been synthesized by a handful plants, fungi, and microalgae. Although the metabolism of fatty acid has been studied for decades, the biosynthesis of NA has yet to be illustrated. Generally, the biosynthesis of NA is considered starting from oleic acid through fatty acid elongation, in which malonyl-CoA and long-chain acyl-CoA are firstly condensed by a rate-limiting enzyme 3-ketoacyl-CoA synthase (KCS). Heterologous expression of kcs gene from high NA producing species in plants and yeast has led to synthesis of NA. Nevertheless, it has also been reported that desaturases in a few plants can catalyze very long-chain saturated fatty acid into NA. This review highlights recent advances in the biosynthesis, the sources, and the biotechnological aspects of NA.

Keywords

Very long-chain monounsaturated fatty acids Synthetic biology Metabolic engineering Cellular engineering 3-Ketoacyl-CoA synthesis 

Notes

Funding information

This project was supported by the National Natural Science Foundation of China (No. 31602154), the Shandong Province Natural Science Major Program (ZR2017ZB0209), and the Shandong Province Natural Science Funds for Young Scholar (Nos. JQ201507 and ZR2017BC108).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethical standards

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

References

  1. Adrio JL (2017) Oleaginous yeasts: promising platforms for the production of oleochemicals and biofuels. Biotechnol Bioeng 114(9):1915–1920.  https://doi.org/10.1002/bit.26337 CrossRefPubMedGoogle Scholar
  2. Amminger GP, Schafer MR, Klier CM, Slavik JM, Holzer I, Holub M, Goldstone S, Whitford TJ, McGorry PD, Berk M (2012) Decreased nervonic acid levels in erythrocyte membranes predict psychosis in help-seeking ultra-high-risk individuals. Mol Psychiatry 17(12):1150–1152.  https://doi.org/10.1038/mp.2011.167 CrossRefPubMedGoogle Scholar
  3. Avalos JL, Fink GR, Stephanopoulos G (2013) Compartmentalization of metabolic pathways in yeast mitochondria improves the production of branched-chain alcohols. Nat Biotechnol 31(4):335–341.  https://doi.org/10.1038/nbt.2509 CrossRefPubMedPubMedCentralGoogle Scholar
  4. Banaś A, Dahlqvist A, Ståhl U, Lenman M, Stymne S (2000) The involvement of phospholipid:diacylglycerol acyltransferases in triacylglycerol production. Biochem Soc Trans 28(6):703–705.  https://doi.org/10.1042/0300-5127:0280703 CrossRefPubMedGoogle Scholar
  5. Bates PD, Durrett TP, Ohlrogge JB, Pollard M (2009) Analysis of acyl fluxes through multiple pathways of triacylglycerol synthesis in developing soybean embryos. Plant Physiol 150(1):55–72.  https://doi.org/10.1104/pp.109.137737 CrossRefPubMedPubMedCentralGoogle Scholar
  6. Baud S, Lepiniec L (2009) Regulation of de novo fatty acid synthesis in maturing oilseeds of Arabidopsis. Plant Physiol Biochem 47(6):448–455.  https://doi.org/10.1016/j.plaphy.2008.12.006 CrossRefPubMedGoogle Scholar
  7. Blacklock BJ, Jaworski JG (2006) Substrate specificity of Arabidopsis 3-ketoacyl-CoA synthases. Biochem Biophys Res Commun 346(2):583–590.  https://doi.org/10.1016/j.bbrc.2006.05.162 CrossRefPubMedGoogle Scholar
  8. Bonaventure G, Salas JJ, Pollard MR, Ohlrogge JB (2003) Disruption of the FATB gene in Arabidopsis demonstrates an essential role of saturated fatty acids in plant growth. Plant Cell 15(4):1020–1033.  https://doi.org/10.1105/tpc.008946 CrossRefPubMedPubMedCentralGoogle Scholar
  9. Chen Y, Kelly EE, Masluk RP, Nelson CL, Cantu DC, Reilly PJ (2011) Structural classification and properties of ketoacyl synthases. Protein Sci 20(10):1659–1667.  https://doi.org/10.1002/pro.712 CrossRefPubMedPubMedCentralGoogle Scholar
  10. Costaglioli P, Joubes K, Garcia C, Stef M, Arveiler B, Lessire R, Garbay B (2005) Profiling candidate genes involved in wax biosynthesis in Arabidopsis thaliana by microarray analysis. BBA-Mol Cell Biol L 1734(3):247–258.  https://doi.org/10.1016/j.bbalip.2005.04.002 CrossRefGoogle Scholar
  11. Coupland K, Raoul, Y. (2001) Nervonic acid derivatives, their preparation and use. PCT: CA2391953Google Scholar
  12. Das S, Roscoe TJ, Delseny M, Srivastava PS, Lakshmikumaran M (2002) Cloning and molecular characterization of the fatty acid Elongase 1 ( FAE 1) gene from high and low erucic acid lines of Brassica campestris and Brassica oleracea. Plant Sci 162(2):245–250.  https://doi.org/10.1016/S0168-9452(01)00556-8 CrossRefGoogle Scholar
  13. Du J, Yuan YB, Si T, Lian JZ, Zhao HM (2012) Customized optimization of metabolic pathways by combinatorial transcriptional engineering. Nucleic Acids Res 40(18):e142.  https://doi.org/10.1093/nar/gks549 CrossRefPubMedPubMedCentralGoogle Scholar
  14. Eiamsa-Ard P, Kanjana-Opas A, Cahoon EB, Chodok P, Kaewsuwan S (2013) Two novel Physcomitrella patens fatty acid elongases (ELOs): identification and functional characterization. Appl Microbiol Biotechnol 97(8):3485–3497.  https://doi.org/10.1007/s00253-012-4556-4 CrossRefPubMedGoogle Scholar
  15. Fan Y, Yuan C, Jin Y, Hu GR, Li FL (2018) Characterization of 3-ketoacyl-CoA synthase in a nervonic acid producing oleaginous microalgae Mychonastes afer. Algal Res 31:225–231.  https://doi.org/10.1016/j.algal.2018.02.017 CrossRefGoogle Scholar
  16. Farquharson J, Jamieson EC, Logan RW, Patrick WJA, Howatson AG, Cockburn F (1996) Docosahexaenoic and nervonic acids in term and preterm infant cerebral white matter. Prenat Neonatal Med 1:234–240Google Scholar
  17. Fillet S, Ronchel C, Callejo C, Fajardo MJ, Moralejo H, Adrio JL (2017) Engineering Rhodosporidium toruloides for the production of very long-chain monounsaturated fatty acid-rich oils. Appl Microbiol Biotechnol 4:1–10.  https://doi.org/10.1007/s00253-017-8461-8 Google Scholar
  18. Gao S, Tong Y, Wen Z, Zhu L, Ge M, Chen D, Jiang Y, Yang S (2016) Multiplex gene editing of the Yarrowia lipolytica genome using the CRISPR-Cas9 system. J Ind Microbiol Biotechnol 43(8):1085–1093.  https://doi.org/10.1007/s10295-016-1789-8 CrossRefPubMedGoogle Scholar
  19. Ghanevati M, Jaworski JG (2002) Engineering and mechanistic studies of the Arabidopsis FAE1 beta-ketoacyl-CoA synthase, FAE1 KCS. Eur J Biochem 269(14):3531–3539.  https://doi.org/10.1046/j.1432-1033.2002.03039.x CrossRefPubMedGoogle Scholar
  20. Guihéneuf F, Khan A, Tran LS (2016) Genetic engineering: a promising tool to engender physiological, biochemical, and molecular stress resilience in green microalgae. Front Plant Sci 7(518):400.  https://doi.org/10.3389/fpls.2016.00400 PubMedPubMedCentralGoogle Scholar
  21. Guo Y, Mietkiewska E, Francis T, Katavic V, Brost JM, Giblin M, Barton DL, Taylor DC (2009) Increase in nervonic acid content in transformed yeast and transgenic plants by introduction of a Lunaria annua L. 3-ketoacyl-CoA synthase (KCS) gene. Plant Mol Biol 69(5):565–575.  https://doi.org/10.1007/s11103-008-9439-9 CrossRefPubMedGoogle Scholar
  22. Guo HS, Zhang YM, Sun XQ, Li MM, Hang YY, Xue JY (2016) Evolution of the KCS gene family in plants: the history of gene duplication, sub/neofunctionalization and redundancy. Mol Genet Genomics 291(2):739–752.  https://doi.org/10.1007/s00438-015-1142-3 CrossRefPubMedGoogle Scholar
  23. Han G, Gable K, Kohlwein SD, Beaudoin F, Napier JA, Dunn TM (2002) The Saccharomyces cerevisiae YBR159w gene encodes the 3-ketoreductase of the microsomal fatty acid elongase. J Biol Chem 277(38):35440–35449.  https://doi.org/10.1074/jbc.M205620200 CrossRefPubMedGoogle Scholar
  24. Han S, Schroeder EA, Silvagarcía CG, Hebestreit K, Mair WB, Brunet A (2017) Mono-unsaturated fatty acids link h3k4me3 modifiers to C. elegans lifespan. Nature 544(7649):185–190.  https://doi.org/10.1038/nature21686 CrossRefPubMedPubMedCentralGoogle Scholar
  25. Haslam TM, Kunst L (2013) Extending the story of very-long-chain fatty acid elongation. Plant Sci 210:93–107.  https://doi.org/10.1016/j.plantsci.2013.05.008 CrossRefPubMedGoogle Scholar
  26. 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):7.  https://doi.org/10.1186/1754-6834-7-7 CrossRefPubMedPubMedCentralGoogle Scholar
  27. Jantzen E, Berdal BP, Omland T (1979) Cellular fatty acid composition of Francisella tularensis. J Clin Microbiol 10(6):928–930PubMedPubMedCentralGoogle Scholar
  28. Joubès J, Raffaele S, Bourdenx B, Garcia C, Laroche-Traineau J, Moreau P, Domergue F, Lessire R (2008) The VLCFA elongase gene family in Arabidopsis thaliana: phylogenetic analysis, 3D modelling and expression profiling. Plant Mol Biol 67(5):547–566.  https://doi.org/10.1007/s11103-008-9339-z CrossRefPubMedGoogle Scholar
  29. Kasai N, Mizushina Y, Sugawara F, Sakaguchi K (2002) Three-dimensional structural model analysis of the binding site of an inhibitor, nervonic acid, of both DNA polymerase β and HIV-1 reverse transcriptase1. J Biochem 132(5):819–828.  https://doi.org/10.1093/oxfordjournals.jbchem.a003292 CrossRefPubMedGoogle Scholar
  30. Kelly DJ, Hughes NJ (2001) The citric acid cycle and fatty acid biosynthesis. In: Mobley HLT, Mendz GL, Hazell SL (eds) Helicobacter pylori: physiology and genetics. Washington (DC)Google Scholar
  31. Kendrick A, Ratledge C (1992) Lipids of selected molds grown for production of n-3 and n-6 polyunsaturated fatty acids. Lipids 27(1):15–20CrossRefPubMedGoogle Scholar
  32. Kennedy EP, Weiss SB (1956) The function of cytidine coenzymes in the biosynthesis of phospholipides. J Biol Chem 222(1):193–214PubMedGoogle Scholar
  33. Klug L, Daum G (2014) Yeast lipid metabolism at a glance. FEMS Yeast Res 14(3):369–388.  https://doi.org/10.1111/1567-1364.12141 CrossRefPubMedGoogle Scholar
  34. Kohlwein SD, Eder S, Oh CS, Martin CE, Gable K, Bacikova D, Dunn T (2001) Tsc13p is required for fatty acid elongation and localizes to a novel structure at the nuclear-vacuolar interface in Saccharomyces cerevisiae. Mol Cell Biol 21(1):109–125.  https://doi.org/10.1128/Mcb.21.1.109-125.2001 CrossRefPubMedPubMedCentralGoogle Scholar
  35. Kunst L, Taylor DC, Underhill EW (1992) Fatty acid elongation in developing seeds of Arabidopsis thaliana. Plant Physiol Biochem 30(4):425–434Google Scholar
  36. Leonard AE, Kelder B, Bobik EG, Chuang LT, Lewis CJ, Kopchick JJ, Mukerji P, Huang YS (2002) Identification and expression of mammalian long-chain PUFA elongation enzymes. Lipids 37(8):733–740.  https://doi.org/10.1007/s11745-002-0955-6 CrossRefPubMedGoogle Scholar
  37. Leonard AE, Pereira SL, Sprecher H, Huang YS (2004) Elongation of long-chain fatty acids. Prog Lipid Res 43(1):36–54.  https://doi.org/10.1016/S0163-7827(03)00040-7 CrossRefPubMedGoogle Scholar
  38. Li X, van Loo EN, Gruber J, Fan J, Guan R, Frentzen M, Stymne S, Zhu LH (2012) Development of ultra-high erucic acid oil in the industrial oil crop Crambe abyssinica. Plant Biotechnol J 10(7):862–870.  https://doi.org/10.1111/j.1467-7652.2012.00709.x CrossRefPubMedGoogle Scholar
  39. Lian JZ, Zhao HM (2015) Recent advances in biosynthesis of fatty acids derived products in Saccharomyces cerevisiae via enhanced supply of precursor metabolites. J Ind Microbiol Biotechnol 42(3):437–451.  https://doi.org/10.1007/s10295-014-1518-0 CrossRefPubMedGoogle Scholar
  40. Liu D, Xiao Y, Evans BS, Zhang F (2015) Negative feedback regulation of fatty acid production based on a malonyl-CoA sensor-actuator. ACS Synth Biol 4(2):132–140.  https://doi.org/10.1021/sb400158w CrossRefPubMedGoogle Scholar
  41. Lu C, Xin Z, Ren Z, Miquel M, Browse J (2009) An enzyme regulating triacylglycerol composition is encoded by the ROD1 gene of Arabidopsis. Proc Natl Acad Sci U S A 106(44):18837–18842.  https://doi.org/10.1073/pnas.0908848106 CrossRefPubMedPubMedCentralGoogle Scholar
  42. Ma BL, Liang SF, Zhao DY, Xu AX, Zhang KJ (2004) Study on plants containing nervonic acid. Acta Botan Boreali-Occiden Sin 24(12):2362–2365.  https://doi.org/10.3321/j.issn:1000-4025.2004.12.031 Google Scholar
  43. Martínez M, Mougan I (2010) Fatty acid composition of human brain phospholipids during normal development. J Neurochem 71(6):2528–2533.  https://doi.org/10.1046/j.1471-4159.1998.71062528.x CrossRefGoogle Scholar
  44. Merchant SS, Prochnik SE, Vallon O, Harris EH, Karpowicz SJ, Witman GB, Terry A, Salamov A, Fritzlaylin LK, Maréchaldrouard L (2007) The Chlamydomonas genome reveals the evolution of key animal and plant functions. Science 318(5848):245–250.  https://doi.org/10.1126/science.1143609 CrossRefPubMedPubMedCentralGoogle Scholar
  45. Merrill AH Jr, Schmelz EM, Wang E, Dillehay DL, Rice LG, Meredith F, Riley RT (1997) Importance of sphingolipids and inhibitors of sphingolipid metabolism as components of animal diets. J Nutr 127(5 Suppl):830S–833SCrossRefPubMedGoogle Scholar
  46. Michalak I, Chojnacka K (2015) Algae as production systems of bioactive compounds. Eng Life Sci 15(2):160–176.  https://doi.org/10.1002/elsc.201400191 CrossRefGoogle Scholar
  47. Millar AA, Kunst L (1997) Very-long-chain fatty acid biosynthesis is controlled through the expression and specificity of the condensing enzyme. Plant J 12(1):121–131.  https://doi.org/10.1046/j.1365-313x.1997.12010121.x CrossRefPubMedGoogle Scholar
  48. Mizushina Y, Ohkubo T, Date T, Yamaguchi T, Saneyoshi M, Sugawara F, Sakaguchi K (1999) Mode analysis of a fatty acid molecule binding to the N-terminal 8-kDa domain of DNA polymerase beta. A 1:1 complex and binding surface. J Biol Chem 274(36):25599–25607.  https://doi.org/10.1074/jbc.274.36.25599 CrossRefPubMedGoogle Scholar
  49. Nichols PD, Palmisano AC, Smith GA, White DC (1986) Lipids of the antarctic sea ice diatom Nitzschia cylindrus. Phytochemistry 25(7):1649–1653.  https://doi.org/10.1016/s0031-9422(00)81228-5 CrossRefGoogle Scholar
  50. Nielsen MK, Arneborg N (2007) The effect of citric acid and pH on growth and metabolism of anaerobic Saccharomyces cerevisiae and Zygosaccharomyces bailii cultures. Food Microbiol 24(1):101–105.  https://doi.org/10.1016/j.fm.2006.03.005 CrossRefPubMedGoogle Scholar
  51. Oh CS, Toke DA, Mandala S, 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 Biol Chem 272(28):17376–17384.  https://doi.org/10.1074/jbc.272.28.17376 CrossRefPubMedGoogle Scholar
  52. Paul S, Gable K, Beaudoin F, Cahoon E, Jaworski J, Napier JA, Dunn TM (2006) Members of the Arabidopsis FAE1-like 3-ketoacyl-CoA synthase gene family substitute for the Elop proteins of Saccharomyces cerevisiae. J Biol Chem 281(14):9018–9029.  https://doi.org/10.1074/jbc.m507723200 CrossRefPubMedGoogle Scholar
  53. Poulos A (1995) Very long chain fatty acids in higher animals—a review. Lipids 30(1):1–14.  https://doi.org/10.1007/bf02537036 CrossRefPubMedGoogle Scholar
  54. Prochnik SE, Umen J, Nedelcu AM, Hallmann A, Miller SM, Nishii I, Ferris P, Kuo A, Mitros T, Fritzlaylin LK (2010) Genomic analysis of organismal complexity in the multicellular green alga Volvox carteri. Science 329(5988):223–226.  https://doi.org/10.1126/science.1188800 CrossRefPubMedPubMedCentralGoogle Scholar
  55. Qiao KJ, Wasylenko TM, Zhou K, Xu P, Stephanopoulos G (2017) Lipid production in Yarrowia lipolytica is maximized by engineering cytosolic redox metabolism. Nat Biotechnol 35(2):173–177.  https://doi.org/10.1038/nbt.3763 CrossRefPubMedGoogle Scholar
  56. Saadaoui I, Ghazal GA, Bounnit T, Khulaifi FA, Jabri HA, Potts M (2016) Evidence of thermo and halotolerant Nannochloris isolate suitable for biodiesel production in qatar culture collection of cyanobacteria and microalgae. Algal Res 14:39–47.  https://doi.org/10.1016/j.algal.2015.12.019 CrossRefGoogle Scholar
  57. Salas JNJ, Ohlrogge JB (2002) Characterization of substrate specificity of plant FatA and FatB acyl-ACP thioesterases. Arch Biochem Biophys 403(1):25–34.  https://doi.org/10.1016/s0003-9861(02)00017-6 CrossRefPubMedGoogle Scholar
  58. Schneiter R, Tatzer V, Gogg G, Leitner E, Kohlwein SD (2000) Elo1p-dependent Carboxy-terminal elongation of C14:1Δ9 to C16:1Δ11 fatty acids in Saccharomyces cerevisiae. J Bacteriol 182(13):3655–3660.  https://doi.org/10.1128/jb.182.13.3655-3660.2000 CrossRefPubMedPubMedCentralGoogle Scholar
  59. Sheng J, Stevens J, Feng X (2016) Pathway compartmentalization in peroxisome of Saccharomyces cerevisiae to produce versatile medium chain fatty alcohols. Sci Rep 6(26884).  https://doi.org/10.1038/srep26884
  60. Shi SB, Zhao HM (2017) Metabolic engineering of oleaginous yeasts for production of fuels and chemicals. Front Microbiol 8(2185).  https://doi.org/10.3389/fmicb.2017.02185
  61. Smith MA, Dauk M, Ramadan H, Yang H, Seamons LE, Haslam RP, Beaudoin F, Ramirezerosa I, Forseille L (2013) Involvement of Arabidopsis ACYL-COENZYME A DESATURASE-LIKE2 (At2g31360) in the biosynthesis of the very-long-chain monounsaturated fatty acid components of membrane lipids. Plant Physiol 161(1):81–96.  https://doi.org/10.1104/pp.112.202325 CrossRefPubMedGoogle Scholar
  62. Strandvik B, Ntoumani E, Lundqvistpersson C, Sabel KG (2016) Long-chain saturated and monounsaturated fatty acids associate with development of premature infants up to 18 months of age. Prostaglandins Leukot Essent Fatty Acids 107:43–49.  https://doi.org/10.1016/j.plefa.2016.01.002 CrossRefPubMedGoogle Scholar
  63. Takeno S, Sakuradani E, Murata S, Inohara-Ochiai M, Kawashima H, Ashikari T, Shimizu S (2005) Molecular evidence that the rate-limiting step for the biosynthesis of arachidonic acid in Mortierella alpina is at the level of an elongase. Lipids 40(1):25–30.  https://doi.org/10.1007/s11745-005-1356-6 CrossRefPubMedGoogle Scholar
  64. Taylor DC, Francis T, Guo Y, Brost JM, Katavic V, Mietkiewska E, Michael GE, Lozinsky S, Hoffman T (2009) Molecular cloning and characterization of a KCS gene from Cardamine graeca and its heterologous expression in Brassica oilseeds to engineer high nervonic acid oils for potential medical and industrial use. Plant Biotechnol J 7(9):925–938.  https://doi.org/10.1111/j.1467-7652.2009.00454.x CrossRefPubMedGoogle Scholar
  65. Tehlivets O, Scheuringer K, Kohlwein SD (2007) Fatty acid synthesis and elongation in yeast. BBA-Mol Cell Biol L 1771(3):255–270.  https://doi.org/10.1016/j.bbalip.2006.07.004 CrossRefGoogle Scholar
  66. Teo WS, Chang MW (2014) Development and characterization of AND-gate dynamic controllers with a modular synthetic GAL1 core promoter in Saccharomyces cerevisiae. Biotechnol Bioeng 111(1):144–151.  https://doi.org/10.1002/bit.25001 CrossRefPubMedGoogle Scholar
  67. Teo WS, Hee KS, Chang MW (2013) Bacterial FadR and synthetic promoters function as modular fatty acid sensor-regulators in Saccharomyces cerevisiae. Eng Life Sci 13(5):456–463.  https://doi.org/10.1002/elsc.201200113 CrossRefGoogle Scholar
  68. Tjellström H, Strawsine M, Silva J, Cahoon EB, Ohlrogge JB (2013) Disruption of plastid acyl:acyl carrier protein synthetases increases medium chain fatty acid accumulation in seeds of transgenic Arabidopsis. FEBS Lett 587(7):936–942.  https://doi.org/10.1016/j.febslet.2013.02.021 CrossRefPubMedGoogle Scholar
  69. Trenkamp S, Martin W, Tietjen K (2004) Specific and differential inhibition of very-long-chain fatty acid elongases from Arabidopsis thaliana by different herbicides. Proc Natl Acad Sci U S A 101(32):11903–11908.  https://doi.org/10.1073/pnas.0404600101 CrossRefPubMedPubMedCentralGoogle Scholar
  70. Tresch S, Heilmann M, Christiansen N, Looser R, Grossmann K (2012) Inhibition of saturated very-long-chain fatty acid biosynthesis by mefluidide and perfluidone, selective inhibitors of 3-ketoacyl-CoA synthases. Phytochemistry 76(12):162–171.  https://doi.org/10.1016/j.phytochem.2011.12.023 CrossRefPubMedGoogle Scholar
  71. Umemoto H, Sawada K, Kurata A, Hamaguchi S, Tsukahara S, Ishiguro T, Kishimoto N (2014) Fermentative production of nervonic acid by Mortierella capitata RD000969. J Oleo Sci 63(7):671–679.  https://doi.org/10.5650/jos.ess14029 CrossRefPubMedGoogle Scholar
  72. Vozella V, Basit A, Misto A, Piomelli D (2017) Age-dependent changes in nervonic acid-containing sphingolipids in mouse hippocampus. Biochim Biophys Acta 1862(12):1502–1511.  https://doi.org/10.1016/j.bbalip.2017.08.008 CrossRefPubMedGoogle Scholar
  73. Wang XY, Fan JS, Wang SQ (2006) Development situation and outlook of nervonic acid plants in China. China Oils Fats 31(3):69–71 http://dx.chinadoi.cn/10.3321/j.issn:1003-7969.2006.03.025 Google Scholar
  74. Wang Q, Lu Y, Xin Y, Wei L, Huang S, Xu J (2016) Genome editing of model oleaginous microalgae Nannochloropsis spp. by CRISPR/Cas9. Plant J 88(6):1071–1081.  https://doi.org/10.1111/tpj.13307 CrossRefPubMedGoogle Scholar
  75. Wassef MK, Ammon V, Wyllie TD (1975) Polar lipids of Macrophomina phaseolina. Lipids 10(3):185–190.  https://doi.org/10.1007/bf02534157 CrossRefGoogle Scholar
  76. Wu GZ, Xue HW (2010) Arabidopsis β-ketoacyl-[acyl carrier protein] synthase i is crucial for fatty acid synthesis and plays a role in chloroplast division and embryo development. Plant Cell 22(11):3726–3744.  https://doi.org/10.1105/tpc.110.075564 CrossRefPubMedPubMedCentralGoogle Scholar
  77. Wynn JP, Ratledge C (2000) Evidence that the rate-limiting step for the biosynthesis of arachidonic acid in Mortierella alpina is at the level of the 18:3 to 20:3 elongase. Microbiol 146(Pt 9):2325–2331.  https://doi.org/10.1099/00221287-146-9-2325 CrossRefGoogle Scholar
  78. Xu P, Gu Q, Wang W, Wong L, Bower AG, Collins CH, Koffas MA (2013) Modular optimization of multi-gene pathways for fatty acids production in E. coli. Nat Commun 4:1409.  https://doi.org/10.1038/ncomms2425 CrossRefPubMedGoogle Scholar
  79. Xu P, Li L, Zhang F, Stephanopoulos G, Koffas M (2014) Improving fatty acids production by engineering dynamic pathway regulation and metabolic control. Proc Natl Acad Sci U S A 111(31):11299–11304.  https://doi.org/10.1073/pnas.1406401111 CrossRefPubMedPubMedCentralGoogle Scholar
  80. Xu P, Qiao KJ, Ahn WS, Stephanopoulos G (2016) Engineering Yarrowia lipolytica as a platform for synthesis of drop-in transportation fuels and oleochemicals. Proc Natl Acad Sci U S A 113(39):10848–10853.  https://doi.org/10.1073/pnas.1607295113 CrossRefPubMedPubMedCentralGoogle Scholar
  81. Xue Z, Sharpe PL, Hong SP, Yadav NS, Xie D, Short DR, Damude HG, Rupert RA, Seip JE, Wang J (2013) Production of omega-3 eicosapentaenoic acid by metabolic engineering of Yarrowia lipolytica. Nat Biotechnol 31(8):734–740.  https://doi.org/10.1038/nbt.2622 CrossRefPubMedGoogle Scholar
  82. Yu T, Zhou YJJ, Wenning L, Liu QL, Krivoruchko A, Siewers V, Nielsen J, David F (2017) Metabolic engineering of Saccharomyces cerevisiae for production of very long chain fatty acid-derived chemicals. Nat Commun 8:15587.  https://doi.org/10.1038/Ncomms15587 CrossRefPubMedPubMedCentralGoogle Scholar
  83. Yuan C, Liu JH, Fan Y, Ren X, Hu GR, Li FL (2011) Mychonastes afer HSO-3-1 as a potential new source of biodiesel. Biotechnol Biofuels 4:47.  https://doi.org/10.1186/1754-6834-4-47 CrossRefPubMedPubMedCentralGoogle Scholar
  84. Yuan C, Zheng YL, Zhang WL, He R, Fan Y, Hu GR, Li FL (2017a) Lipid accumulation and anti-rotifer robustness of microalgal strains isolated from eastern China. J Appl Phycol 29:2789–2800.  https://doi.org/10.1007/s10811-017-1167-6 CrossRefGoogle Scholar
  85. Yuan C, Xu K, Sun J, Hu GR, Li FL (2017b) Ammonium, nitrate, and urea play different roles for lipid accumulation in the nervonic acid—producing microalgae Mychonastes afer HSO-3-1. J Appl Phycol.  https://doi.org/10.1007/s10811-017-1308-y
  86. Zakim D, Herman RH (1997) Regulation of fatty acid synthesis. Annu Rev Plant Phys 48:109–136.  https://doi.org/10.1146/annurev.arplant.48.1.109 CrossRefGoogle Scholar
  87. Zhou YJ, Buijs NA, Zhu Z, Qin J, Siewers V, Nielsen J (2016) Production of fatty acid-derived oleochemicals and biofuels by synthetic yeast cell factories. Nat Commun 7:11709.  https://doi.org/10.1038/ncomms11709 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Key Laboratory of Biofuels, Shandong Provincial Key Laboratory of Synthetic Biology, Qingdao Engineering Laboratory of Single Cell Oil, Qingdao Institute of Bioenergy and Bioprocess TechnologyChinese Academy of SciencesQingdaoPeople’s Republic of China

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