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Three, two, one yeast fatty acid desaturases: regulation and function

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Abstract

Fatty acid composition of biological membranes functionally adapts to environmental conditions by changing its composition through the activity of lipid biosynthetic enzymes, including the fatty acid desaturases. Three major desaturases are present in yeasts, responsible for the generation of double bonds in position C9–C10, C12–C13 and C15–C16 of the carbon backbone. In this review, we will report data addressed to define the functional role of basidiomycete and ascomycete yeast desaturase enzymes in response to various external signals and the regulation of the expression of their corresponding genes. Many yeast species have the complete set of three desaturases; however, only the Δ9 desaturase seems to be necessary and sufficient to ensure yeast viability. The evolutionary issue of this observation will be discussed.

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References

  • Alexandre H, Rousseaux I, Charpentier C (1994) Relationship between ethanol tolerance, lipid composition and plasma membrane fluidity in Saccharomyces cerevisiae and Kloeckera apiculata. FEMS Microbiol Lett 124:17–22. doi:10.1111/j.1574-6968.1994.tb07255.x

    Article  CAS  Google Scholar 

  • Bossie MA, Martin CE (1989) Nutritional regulation of yeast ∆-9 fatty acid desaturase activity. J Bacteriol 171:6409–6413

    Article  CAS  Google Scholar 

  • Buček A, Matouškova P, Sychrová H, PichováI, Hrušková-Heidingsfeldová O (2014) ∆12-fatty acid desaturase from Candida parapsilosis is a multifunctional desaturase producing a range of polyunsaturated and hydroxylated fatty acids. PLoS ONE 9:e93322. doi:10.1371/journal.pone.0093322

    Article  Google Scholar 

  • Burr R, Stewart EV, Shao W, Zhao S, Hannibal-Bach HK, Ejsing CS, Espenshade PJ (2016) Mga2 transcription factor regulates an Oxygen-responsive lipid homeostasis pathway in fission yeast. J Biol Chem 291:12171–12183. doi:10.1074/jbcM116.723650

    Article  CAS  Google Scholar 

  • Butler G et al (2009) Evolution of pathogenicity and sexual reproduction in eight Candida genomes. Nature 459:657–662. doi:10.1038/nature08064

    Article  CAS  Google Scholar 

  • Chellappa R, Kandasamy P, Oh CS, Jiang Y, vemula M, Martin CE (2001) The membrane proteins, Spt23p and Mga2p, play distinct roles in the activation of Saccharomyces cerevisiae OLE1 gene expression. Fatty acid-mediated regulation of Mga2p activity is independent of its proteolytic processing into a soluble transcription activator. J Biol Chem 276:43548–43556. doi:10.1074/jbc.M107845200

    Article  CAS  Google Scholar 

  • Choi J-Y, Stukey J, Hwang S-Y, Martin CE (1996) Regulatory elements that control transcription activation and unsaturated fatty acid-mediated repression of the Saccharomyces cerevisiae OLE1 gene. J Biol Chem 271:3581-35-89

    Google Scholar 

  • Cui J, He S, Ji X, Lin L, Wei Y, Zhang Q (2016) Identification and characterization of a novel bifunctional ∆12/∆15 -fatty acid desaturase gene from Rhodosporidium kratochvilovae. Biotechnol Lett 38:1155–1164. doi:10.1007/s10529-016-2090-7

    Article  CAS  Google Scholar 

  • De Angelis L, Rinaldi T, Cirigliano A, Bello C, Reverberi M, Amaretti A, Montanari A, Santomartino R, Raimondi S, Gonzalez A, Bianchi MM (2016) Functional roles of the fatty acid desaturases encoded by KlOLE1, FAD2 and FAD3 in the yeast Kluyveromyces lactis. Microbiology 162:1435–1445. doi:10.1099/mic0.000315

    Article  Google Scholar 

  • Hashimoto K, Yoshizawa AC, Okuda S, Kuma K, Goto S, Kanehisa M (2008) The repertoire of desaturases and elongases reveals fatty acid variations in 56 eukaryotic genomes. J Lipid Res 49:183–191. doi:10.1194//jlr.M700377-JLR200

    Article  CAS  Google Scholar 

  • He J, Yang Z, Hu B, Ji X, Wei Y, Lin L, Zhang Q (2015) Correlation of unsaturated fatty acids with the cold adaptation of Rhodotorula glutinis. Yeast 32:683–690. doi:10.1002/yea.3095

    Article  CAS  Google Scholar 

  • Hong H, Datla N, Reed DW, Covello PS, MacKenzie SL, Qiu X (2002a) High-level production of gamma-linolenic acid in Brassica juncea using a delta6 desaturase from Phytium irregulare. Plant Physiol 129:354–362

    Article  CAS  Google Scholar 

  • Hong H, Datla N, MacKenzie SL, Qiu X (2002b) Isolation and characterization of delta5 FA desaturase from Phytium irregulare by heterologous expression in Saccharomyces cerevisiae and oilseed crops. Lipids 37:863–868

    Article  CAS  Google Scholar 

  • Hoppe T, Matuschewski K, Rape M, Schlenker S, Ulrich HD, Jentsch S (2000) Activation of a membrane-bound transcription factor by regulated ubiquitin/proteasome-dependent processing. Cell 102:577–586. doi:10.1016/S0092-8674(00)00080-5

    Article  CAS  Google Scholar 

  • Huerta-Cepas J, Capella-Gutierrez S, Pryszcz LP, Denisov I, Kormes D, Marcet-Houben M, Gabaldón T (2011) PhylomeDB v3.0: an expanding repository of genome-wide collections of trees, alignements and phylogeny-based orthology and paralogy predictions. Nucleic Acid Res 39:D556–D560. doi:10.1093/nar/gkq1109

    Article  CAS  Google Scholar 

  • Huerta-Cepas J, Capella-Gutiérrez S, Pryszcz LP, Marcet-Houben M, Gabaldón T (2014) PhylomeDB v4: zooming into the plurality of evolutionary histories of a genome. Nucleic Acids Res 42:D897–D902. doi:10.1093/nar/gkt1177

    Article  CAS  Google Scholar 

  • Jiang Y, Vasconcelles MJ, Wretzel S, Light A, Martin CE, Goldberg MA (2001) MGA2 is involved in the low-oxygen response element-dependent hypoxic induction of genes in Saccharomyces cerevisiae. Mol Cell Biol 21:6161–6169. doi:10.1128/MCB.21.18.6161-6169.2001

    Article  CAS  Google Scholar 

  • Jiang Y, Vasconcelles MJ, Wretzel S, Light A, Gilooy L, McDaid K, Oh C-S, Martin CE, Goldberg MA (2002) Mga2p processing by hypoxia and unsaturated fatty acids in Saccharomyces cerevisiae: impact on lore-dependent gene expression. Eukaryot Cell 1:481–490. doi:10.1128/EC.1.3.481-490.2002

    Article  CAS  Google Scholar 

  • Kainou K, Kamisaka Y, Kimura K, Uemura H (2006) Isolation of delta12 and omega3-fatty acid desaturase genes from the yeastKluyveromyces lactisand their heterologous expression to produce linoleic and alpha-linolenic acids in Saccharomyces cerevisiae. Yeast 23:605–612

    Article  CAS  Google Scholar 

  • Kajiwara S (2002) Molecular cloning and characterization of the delta9 fatty acid desaturase gene and its promoter region from Saccharomyces kluyveri. FEMS Yeast Res 2:333–339. doi:10.1016/S1567-1356(02)00088-0

    CAS  Google Scholar 

  • Kandasamy P, Vemula M, Oh CS, Chellappa R, Martin CE (2004) Regulation of unsaturated fatty acid biosynthesis in Saccharomyces: the endoplasmic reticulum membrane protein, Mga2p, a transcription activator of the OLE1 gene, regulates the stability of the OLE1 mRNA through exosome-mediated mechanisms. J Biol Chem 279:36586–36592. doi:10.1074/jbc.M401557200

    Article  CAS  Google Scholar 

  • Kimura K, Tomita N, Uemura H, Aki T, Ono K, Kamisaka Y (2009) Improvement of stearidonic acid production in oleaginous Saccharomyces cerevisiae. Biosci Biotechnol Biochem 73:1447–1449

    Article  CAS  Google Scholar 

  • Krishnamurthy S, Plaine A, Albert J, Prasad T, Prasad R, Ernst JF (2004) Dosage-dependent functions of fatty acid desaturase Ole1p in growth and morphogenesis of Candida albicans. Microbiology 150:1091–2003. doi:10.1099/mic.027029-0

    Article  Google Scholar 

  • Kwast KE, Burke PV, Staahl BT Poyton RO (1999) Oxygen sensing in yeast: evidence for the involvement of the respiratory chain in regulating the transcription of a subset of hypoxic genes. Proc Natl Acad Sci USA 96:5446–5451.

    Article  CAS  Google Scholar 

  • Laoteng K, Mannontarat R, Tanticharoen M, Cheevadhanarak S (2000) Delta6-desaturase of Mucor rouxii with high similarity to plant delta 6-desaturase and its heterologous expression in Saccharomyces cerevisiae. Biochem Biophys Res Commun 279:17–22

    Article  CAS  Google Scholar 

  • Ledesma-Amaro R, Santos M-A, Jiménez A, Revuelta JL (2014) Tuning single-cell oil production in Ashbya gossypii by engineering the elongation and desaturation systems. Biotechnol Bioeng 111:1782–1791. doi:10.1002/bit.25245

    Article  CAS  Google Scholar 

  • Li YT, Li MT, Fu CH, Zhou PP, Liu JM, Yu LJ (2009) Improvement of arachidonic acid and eicosapentaenoic acid production by increasing the copy number of the genes encoding fatty acid desaturases and elongases into Pichia pastoris. Biotechnol Lett 31:1011–1017. doi:10.1007/s10529-009-9970-z

    Article  CAS  Google Scholar 

  • Liu L, Markham K, Blazeck J, Zhou N, Leon D, Otoupal P, Alper HS (2015) Surveying the lipogenesis landscape in Yarrowia lipolytica through understanding the function of a Mga2p regulatory protein mutant. Metabol Eng 31:102–111. doi:10.1016/j.ymben.2015.07.004.

    Article  Google Scholar 

  • Los DA, Murata N (1998) Structure and expression of fatty acid desaturases. Biochim Biophys Acta 1394:3–15

    Article  CAS  Google Scholar 

  • Lu SF, Tolstorukov II, Anamnart S, Kaneko Y, Harashima S (2000) Cloning, sequencing and functional analysis of H-OLE1 gene encoding delta9-fatty acid desaturase in Hansenula polymorpha. Appl Microbiol Biotechnol 54:499–509

    Article  CAS  Google Scholar 

  • Mallet S, Weiss S, Jacques N, Leh-Louis V, Sacerdot C, Casaregola S (2012) Insights into the life cycle of yeasts from the CTG clade revealed by the analysis of the Millerozyma (Pichia) farinosa species complex. PLoS ONE 7:e35842. doi:10.1371/journal.pone.0035842

    Article  CAS  Google Scholar 

  • Marcet-Houben M, Gabaldón T (2015) Beyond the Whole-genome duplication: phylogenetic evidence of an ancient interspecies hybridization in baker’s yeast lineage. PLoS Biol 13:e1002220. doi:10.1371/journal.pbio.1002220

    Article  Google Scholar 

  • Martin CE, Oh C-S, Jiang Y (2007) Regulation of long chain unsaturated fatty acids synthesis in yeast. Biochim Biophys Acta 1771:271–285. doi:10.1016/j.bbalip.2006.06.010

    Article  CAS  Google Scholar 

  • McDonough VM, Stukey JE, Martin CE (1992) Specificity of unsaturated fatty acid-regulated expression of the Saccharomyces cerevisiae OLE1 gene. J Biol Chem 267:5931–5936

    CAS  Google Scholar 

  • Meesapyodsuk D, Chen Y, Ng SH, Chen J, Qiu X (2015) Metabolic engineering of Pichia pastoris to produce ricinoleic acid, a hydroxyl fatty acid of industrial importance. J Lipid Res 56:2102–2109. doi:10.1194/jlr.M060954

    Article  CAS  Google Scholar 

  • Meesters PA, Eggink G (1996) Isolation and characterization of a delta-9 fatty acid desaturase gene from the oleaginous yeast Chryptococcus curvatus CBS 570. Yeast 12:723–730

    Article  CAS  Google Scholar 

  • Michaelson LV, Lazarus CM, Griffiths G, Napier JA, Stobart AK (1998) Isolation of Delta5-fatty acid desaturase gene from Mortierella alpine. J Biol Chem 273:19055–19059

    Article  CAS  Google Scholar 

  • Micolonghi C, Ottaviano D, Di Silvio E, Damato G, Heipieper HJ, Bianchi MM (2012) A dual signaling pathway for the hypoxic expression of lipid genes, dependent on the glucose sensor Rag4, is revealed by the analysis of the KlMGA2 gene in Kluyveromyces lactis. Microbiology 158:1734–1744. doi:10.1099/mic.0.059402-0

    Article  CAS  Google Scholar 

  • Mohamed AH, Chirala SS, Mody NH, Huang W-Y, Wakil SJ (1988) Primary structure of the multifunctional α subunit protein of yeast fatty acid synthase derived from FAS2 gene sequence. J Biol Chem 263:12315–12325

    CAS  Google Scholar 

  • Morales L et al (2013) Complete DNA sequence of Kuraishia capsulata illustrates novel genomic features among budding yeasts (Saccharomycotina). Genome Biol Evol 5:2524–2539. doi:10.1093/gbe/evt201

    Article  Google Scholar 

  • Murayama SY, Negishi Y, Umeyama T, Kaneko A, Oura T, Niimi M, Ubukata K, Kajiwara S (2006) Construction and functional analysis of fatty acid desaturase gene disruptants incandida albicans. Microbiology 152:1551–1558. doi:10.1099/mic.0.28751-0

    Article  CAS  Google Scholar 

  • Nakagawa Y, Sugioka S, Kaneko Y, Harashima S (2001) O2R, a novel regulatory element mediating Rox1p- independent O 2 and unsaturated fatty acid repression of OLE1 in Saccharomyces cerevisiae. J Bacteriol 183:745–751

    Article  CAS  Google Scholar 

  • Nakagawa Y, Sakumoto N, Kaneko Y, Harashima S (2002) Mga2p is a putative sensor for low temperature and oxygen to induce OLE1 transcription in Saccharomyces cerevisiae. Biochem Biophys Res Comm 271:707–713

    Article  Google Scholar 

  • Nguyen LN, Gacser A, Nosanchuk JD (2011) The stearoyl-coenzyme A desaturase is essential for virulence and membrane stress in Candida parapsilosis through unsaturated fatty acid production. Infect Immun 79:136–145. doi:10.1128/IAI.00753-10

    Article  CAS  Google Scholar 

  • Oh C-S, Martin CE (2006) Candida albicans Spt23p controls the expression of Ole1p ∆9 fatty acid desaturase and regulates unsaturated fatty acid biosynthesis. J Biol Chem 281:7030–7039. doi:10.1074/jbcM510746200

    Article  CAS  Google Scholar 

  • 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 272:17376–17384

    Article  CAS  Google Scholar 

  • Ottaviano D, Montanari A, De Angelis L, Santomartino R, Visca A, Brambilla L, Rinaldi T, bello C, Reverberi M, Bianchi MM (2015) Unsaturated fatty acids-dependent linkage between respiration and fermentation revealed by deletion of hypoxic regulatory KlMGA2 gene in the facultative anaerobe-respiratory yeast Kluyveromyces lactis. FEMS Yeast Res 15:fov028. doi:10.1093/femsyr/fov028.

    Article  Google Scholar 

  • Oura T, Kajiwara S (2004) Saccharomyces kluyverii FAD3 encodes an ω3 fatty acid desaturase. Microbiology 150:1983–1990. doi:10.1099/mic.0.27049-0

    Article  CAS  Google Scholar 

  • Pereira L, Silva S, Ribeiro B, Henriques M, Azeredo J (2015) Influence of glucose concentration on the structure and quality of biofilms formed by Candida parapsilosis. FEMS Yeast Res 15:fov043. doi:10.1093/femsyr/fov043.

    Article  Google Scholar 

  • Piškur J, Langkjær RB (2004) Yeast genome sequencing: the power of comparative genomics. Mol Microbiol 53:381–389. doi:10.1111/j.1365-2958.2004.04182.x

    Article  Google Scholar 

  • Qiao K, Imam Abidi SH, Liu H, Zhang H, Chakraborty S, Watson N, Kumaran Ajikumar P, Stephanopulos G (2015) Engineering lipid overproduction in the oleaginous yeast Yarrowia lipolytica. Metab Eng 29:56–65. doi:10.1016/j.ymben.2015.02.005

    Article  CAS  Google Scholar 

  • Sakurdani E, Kobayashi M, Shimizu S (1999) Delta6-fatty acid desaturase from an arachidonic acid-producing Mortierella fungus. Gene cloning and its heterologous expression in a fungus, Aspergillus. Gene 238:445–453

    Article  Google Scholar 

  • Sangwallek J, Kaneko Y, Tsukamoto T, Marui M, Sugiyama M, Ono H, Bamba T, Fukusaki E, Harashima S (2014) Cloning and functional analysis of HpFAD2 and HpFAD3 genes encoding ∆12- and ∆15-fatty acid desaturases in Hansenula polymorpha. Gene 533:110–118. doi:10.1016/j.gene.2013.09.115

    Article  CAS  Google Scholar 

  • Stewart LC, Yaffe MP (1991) A role for unsaturated fatty acids in mitochondrial movement and inheritance. J Cell Biol 115:1249–1257

    Article  CAS  Google Scholar 

  • Stukey JE, McDonough VM, Martin CE (1989) Isolation and characterization of OLE1, a gene affecting fatty acid desaturation from Saccharomyces cerevisiae. J Biol Chem 264:16537–16544

    CAS  Google Scholar 

  • Toke DA, Martin CE (1996) Isolation and characterization of a gene affecting fatty acid elongation in Saccharomyces cerevisiae. J Biol Chem 271:18413–18422

    Article  CAS  Google Scholar 

  • Vasconcelles MJ, Jiang Y, McDaid K, Gilooy L, Wretzel S, Porter DL, Martin ME, Goldberg MA (2001) Identification and characterization of a low oxygen response element involved in the hypoxic induction of a family of Saccharomyces cerevisiae genes. J Biol Chem 276:14374–14384

    CAS  Google Scholar 

  • Wan X, Zhang Y, Wang P, Huang F, Chen H, Jiang M (2009) Production of gamma-linolenic acid in Pichia pastoris by expression of a delta-6 desaturase gene from Cunninghamella echinulata. J Microbiol Biotechnol 19:1098–1102

    Article  CAS  Google Scholar 

  • Wang M, Chen H, Gu Z, Zhang H, Chen W, Chen YQ (2013) ω3 fatty acid desaturases from microorganisms: structure, function, evolution and biotechnological use. Appl Microbiol Biotechnol 97:10255–10262. doi:10.1007/s00253-013-5336-5

    Article  CAS  Google Scholar 

  • Wang Y, Zhang S, PÓ§tter M, Sun W, Li L, Yang X, Jiao X, Zhao ZK (2016) Overexpression of ∆12-fatty acid desaturasein the oleaginous yeast Rhodosporidium toruloides for production of linoleic acid-rich lipids. Appl Biochem Biotechnol 180:1497–1507. doi:10.1007/s12010-016-2182-9

    Article  CAS  Google Scholar 

  • Watanabe K, Oura T, Sakai H, Kajiwara S (2004) Yeast ∆12 fatty acid desaturase: gene cloning, expression and function. Biosci Biotechnol Biochem 68:721–727

    Article  CAS  Google Scholar 

  • Yu A-Q, Shi T-L, Zhang B, Xing L-J, Li M-C (2012a) Transcriptional regulation of desaturase genes in Pichia pastoris GS115. Lipids 47:1099–1108. doi:10.1007/s11745-012-3712-z

    Article  CAS  Google Scholar 

  • Yu A-Q, Zhu J-C, Zhang B, Xing L-J, Li M-C (2012b) Knockout of fatty acid desaturase genes in Pichia pastoris GS115 and its effect on the fatty acid biosynthesis and physiological consequences. Arch Microbiol 194:1023–1032. doi:10.1007/s00203-012-0835-9

    CAS  Google Scholar 

  • Zhang S, Skalsky Y, Garfinkel DJ (1999) MGA2orSPT23is required for transcription of the delta9 fatty acid desaturase gene, OLE1, and nuclear membrane integrity in Saccharomyces cerevisiae. Genetics 151:473–483

    CAS  Google Scholar 

  • Zhang M, Liu Z, Yu Q, Mao J, Zhang B, Xing L, Li M (2015) Deletion of genes encoding fatty acid desaturases leads to alteration is stress sensitivity in Pichia pastoris. FEMS Yeast Res 15:fov020. doi:10.1093/femsyr/fov020

    Google Scholar 

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Acknowledgements

This work was supported by Sapienza Università di Roma (C26A147BSJ) and by Ministero Affari Esteri e Cooperazione Internazionale, Direzione generale per la Promozione del Sistema Paese (MX14MO08, PGR00208 and PGR00209).

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Correspondence to Michele M. Bianchi.

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Santomartino, R., Riego-Ruiz, L. & Bianchi, M.M. Three, two, one yeast fatty acid desaturases: regulation and function. World J Microbiol Biotechnol 33, 89 (2017). https://doi.org/10.1007/s11274-017-2257-y

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