Abstract
High energy prices, depletion of crude oil supplies, and price imbalance created by the increasing demand of plant oils or animal fat for biodiesel and specific lipid derivatives such as lubricants, adhesives, and plastics have given rise to heated debates on land-use practices and to environmental concerns about oil production strategies. However, commercialization of microbial oils with similar composition and energy value to plant and animal oils could have many advantages, such as being non-competitive with food, having shorter process cycle and being independent of season and climate factors. This review focuses on the ongoing research on different oleaginous yeasts producing high added value lipids and on the prospects of such microbial oils to be used in different biotechnological processes and applications. It covers the basic biochemical mechanisms of lipid synthesis and accumulation in these organisms, along with the latest insights on the metabolic processes involved. The key elements of lipid accumulation, the mechanisms suspected to confer the oleaginous character of the cell, and the potential metabolic routes enhancing lipid production are also extensively discussed.
Similar content being viewed by others
References
Ailey R, Madden K, Trueheart J (2007) Production of carotenoids in oleaginous yeast and fungi. United States Patent No 20070015237
Amaretti A, Raimondi S, Sala M, Roncaglia L, De Lucia M, Leonardi A, Rossi M (2010) Single cell oils from the cold adapted oleaginous yeast Rhotorula glacialis DBVPG 4785. Micr Cell Fact 9:73
Athenstaedt K, Daum G (2006) The life cycle of neutral lipids: synthesis, storage and degradation. Cell Mol Life Sci 63:1355–1369
Athenstaedt K, Jolivet P, Boulard C, Zivy M, Negroni L, Nicaud JM, Chardot T (2006) Lipid particle composition of the yeast Yarrowia lipolytica depends on the carbon source. Proteomics 6(5):1450–1459
Beckman M (2006) Cell biology. Great balls of fat. Science 311(5765):1232–1234
Belcher LA, Mackenzie SA, Donner M, Sykes GP, Frame SR, Gillies PJ (2011) Safety assessment of EPA-rich triglyceride oil produced from yeast: genotoxicity and 28-day oral toxicity in rats. Regul Toxicol Pharmacol 59:53–63
Beopoulos A, Mrozova Z, Thevenieau F, Le Dall MT, Hapala I, Papanikolaou S, Chardot T, Nicaud JM (2008) Control of lipid accumulation in the yeast Yarrowia lipolytica. Appl Environ Microbiol 74:7779–7789
Beopoulos A, Cescut J, Haddouche R, Uribelarrea JL, Molina-Jouve C, Nicaud JM (2009a) Yarrowia lipolytica as a model for bio-oil production. Prog Lipid Res 48:375–387
Beopoulos A, Desfougeres T, Sabirova J, Zinjarde S, Neuveglise C, Nicaud JM (2009b) The hydrocarbon-degrading oleaginous yeast Yarrowia lipolytica. In: Timmis KN (ed) Handbook of hydrocarbon and lipid microbiology. Springer, Germany
Biobel F, Erdmann R (1996) Identification of a yeast peroxisomal member of the family of AMP-binding proteins. Eur J Biochem 340:468–476
Black PN, DiRusso CC (2007) Vectorial acylation: linking fatty acid transport and activation to metabolic trafficking. Novartis Found Symp 286:127–138, discussion 138–141, 162–123, 196–203
Boer E, Steinborn G, Kunze G, Gellissen G (2007) Yeast expression platforms. Appl Microbiol Biotechnol 77:513–523
Boles E, de Jong-Gubbels P, Pronk JT (1998) Identification and characterization of mae1, the Saccharomyces cerevisiae structural gene encoding mitochondrial malic enzyme. J Bacteriol 180:2875–2882
Botham PA, Ratledge C (1979) A biochemical explanation for lipid accumulation in Candida 107 and other oleaginous micro-organisms. J Gen Microbiol 114:361–375
Brown DA (2001) Lipid droplets: proteins floating on a pool of fat. Curr Biol 11:446–449
Chen X, Li Z, Zhang X, Hu F, Ryu DD, Bao J (2009) Screening of oleaginous yeast strains tolerant to lignocellulose degradation compounds. Appl Biochem Biotechnol 159:591–604
Chirala SS (1992) Coordinated regulation and inositol-mediated and fatty acid-mediated repression of fatty acid synthase genes in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 89:10232–10236
Coleman RA, Lee DP (2004) Enzymes of triacylglycerol synthesis and their regulation. Prog Lipid Res 43:134–176
Czabany T, Athenstaedt K, Daum G (2007) Synthesis, storage and degradation of neutral lipids in yeasts. Biochim Biophys Acta 1771:299–309
Dahlqvist A, Stahl U, Lenman M, Banas A, Lee M, Sandager L, Ronne H, Stymne S (2000) Phospholipid:diacylglycerol acyltransferase: an enzyme that catalyzes the acyl-CoA-independent formation of triacylglycerol in yeast and plants. Proc Natl Acad Sci USA 97:6487–6492
Damude HG, Zhang H, Farrall L, Ripp KG, Tomb JF, Hollerbach D, Yadav NS (2006) Identification of bifunctional delta12/omega3 fatty acid desaturases for improving the ratio of omega3 to omega6 fatty acids in microbes and plants. Proc Natl Acad Sci USA 103:9446–9451
Daum G, Wagner A, Czabany T, Athenstaedt K (2007) Dynamics of neutral lipid storage and mobilization in the yeast. Biochimie 89:243–248
Dell'Angelica EC, Stella CA, Ermacora MR, Ramos EH, Santome JA (1992) Study on fatty acid binding by proteins in yeast. Dissimilar results in Saccharomyces cerevisiae and Yarrowia lipolytica. Comp Biochem Physiol B 102:261–265
Denic V, Weissman JS (2007) A molecular caliper mechanism for determining very long-chain fatty acid length. Cell 130:663–677
DiRusso CC, Black PN (1999) Long-chain fatty acid transport in bacteria and yeast. Paradigms for defining the mechanism underlying this protein-mediated process. Mol Cell Biochem 192(1–2):41–52
Dujon B, Sherman D, Fischer G, Durrens P, Casaregola S, Lafontaine I, de Montigny J, Marck C, Neuveglise C, Talla E, Goffard N, Frangeul L, Aigle M, Anthouard V, Babour A, Barbe V, Barnay S, Blanchin S, Beckerich J-M, Beyne E, Bleykasten C, Boisrame A, Boyer J, Cattolico L, Confanioleri F, de Daruvar A, Despons L, Fabre E, Fairhead C, Ferry-Dumazet H, Groppi A, Hantraye F, Hennequin C, Jauniaux N, Joyet P, Kachouri R, Kerrest A, Koszul R, Lemaire M, Lesur I, Ma L, Muller H, Nicaud J-M, Nikolski M, Oztas S, Ozier-Kalogeropoulos O, Pellenz S, Potier S, Richard G-F, Straub M-L, Suleau A, Swennen D, Tekaia F, Wesolowski-Louvel M, Westhof E, Wirth B, Zeniou-Meyer M, Zivanovic I, Bolotin-Fukuhara M, Thierry A, Bouchier C, Caudron B, Scarpelli C, Gaillardin C, Weissenbach J, Wincker P, Souciet J-L (2004) Genome evolution in yeasts. Nature 430(6995):35–44
Eschenfeldt WH, Zhang Y, Samaha H, Stols L, Eirich LD, Wilson CR, Donnelly MI (2003) Transformation of fatty acids catalyzed by cytochrome p450 monooxygenase enzymes of Candida tropicalis. Appl Environ Microbiol 69:5992–5999
Faergeman NJ, DiRusso CC, Elberger A, Knudsen J, Black PN (1997) Disruption of the Saccharomyces cerevisiae homologue to the murine fatty acid transport protein impairs uptake and growth on long-chain fatty acids. J Biol Chem 272:8531–8538
Ferreyra RG, Burgardt NI, Milikowski D, Melen G, Kornblihtt AR, Dell' Angelica EC, Santome JA, Ermacora MR (2006) A yeast sterol carrier protein with fatty-acid and fatty-acyl-CoA binding activity. Arch Biochem Biophys 453:197–206
Fickers P, Benetti PH, Wache Y, Marty A, Mauersberger S, Smit MS, Nicaud JM (2005a) Hydrophobic substrate utilisation by the yeast Yarrowia lipolytica, and its potential applications. FEMS Yeast Res 5(6–7):527–543
Fickers P, Fudalej F, Le Dall MT, Casaregola S, Gaillardin C, Thonart P, Nicaud JM (2005b) Identification and characterisation of lip7 and lip8 genes encoding two extracellular triacylglycerol lipases in the yeast Yarrowia lipolytica. Fungal Genet Biol 42:264–274
Francois J, Parrou JL (2001) Reserve carbohydrates metabolism in the yeast Saccharomyces cerevisiae. FEMS Microbiol Rev 25:125–145
Fujimoto T, Ohsaki Y, Cheng J, Suzuki M, Shinohara Y (2008) Lipid droplets: a classic organelle with new outfits. Histochem Cell Biol 130:263–279
Gangar A, Karande AA, Rajasekharan R (2001) Isolation and localization of a cytosolic 10 s triacylglycerol biosynthetic multienzyme complex from oleaginous yeast. J Biol Chem 276:10290–10298
Garcia Sanchez R, Karhumaa K, Fonseca C, Sanchez Nogue V, Almeida JR, Larsson CU, Bengtsson O, Bettiga M, Hahn-Hagerdal B, Gorwa-Grauslund MF (2010) Improved xylose and arabinose utilization by an industrial recombinant Saccharomyces cerevisiae strain using evolutionary engineering. Biotechnol Biofuels 3:13
Gaspar ML, Hofbauer HF, Kohlwein SD, Henry SA (2011) Coordination of storage lipid synthesis and membrane biogenesis: evidence for cross-talk between triacylglycerol metabolism and phosphatidylinositol synthesis. J Biol Chem 286:1696–1708
Goodrich-Tanrikulu M, Stafford AE, Lin JT, Makapugay MI, Fuller G, McKeon TA (1994) Fatty acid biosynthesis in novel ufa mutants of Neurospora crassa. Microbiol 140(10):2683–2690
Granger L (1992) Caractérisation cinétique et stoechiometrique de la synthèse d’acide gras chez Rhodotorula glutinis. Institut National des sciences appliquées de Toulouse, Toulouse
Gui M, Lee KT, Bhatia S (2008) Feasibility of edible oil vs. non-edible oil vs. waste edible oil as biodiesel feedstock. Energy 33:1646–1653
Guo T, Kit YY, Nicaud JM, Le Dall MT, Sears SK, Vali H, Chan H, Rachubinski RA, Titorenko VI (2003) Peroxisome division in the yeast Yarrowia lipolytica is regulated by a signal from inside the peroxisome. J Cell Biol 162:1255–1266
Haddouche R, Delessert S, Sabirova J, Neuveglise C, Poirier Y, Nicaud JM (2010) Roles of multiple acyl-CoA oxidases in the routing of carbon flow towards beta-oxidation and polyhydroxyalkanoate biosynthesis in Yarrowia lipolytica. FEMS Yeast Res 10:917–927
Hasslacher M, Ivessa AS, Paltauf F, Kohlwein SD (1993) Acetyl-CoA carboxylase from yeast is an essential enzyme and is regulated by factors that control phospholipid metabolism. J Biol Chem 268:10946–10952
Heier C, Taschler U, Rengachari S, Oberer M, Wolinski H, Natter K, Kohlwein SD, Leber R, Zimmermann R (2010) Identification of yju3p as functional orthologue of mammalian monoglyceride lipase in the yeast Saccharomyces cerevisiae. Biochim Biophys Acta 1801:1063–1071
Hettema EH, Tabak HF (2000) Transport of fatty acids and metabolites across the peroxisomal membrane. Biochim Biophys Acta 1486:18–27
Hettema EH, van Roermund CW, Distel B, van den Berg M, Vilela C, Rodrigues-Pousada C, Wanders RJ, Tabak HF (1996) The abc transporter proteins pat1 and pat2 are required for import of long-chain fatty acids into peroxisomes of Saccharomyces cerevisiae. EMBO J 15:3813–3822
Hiltunen JK, Mursula AM, Rottensteiner H, Wierenga RK, Kastaniotis AJ, Gurvitz A (2003) The biochemistry of peroxisomal [beta]-oxidation in the yeast Saccharomyces cerevisiae. FEMS Microbiol Rev 27:35–64
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 284:9011–9015
Holdsworth JE, Veenhuis M, Ratledge C (1988) Enzyme activities in oleaginous yeasts accumulating and utilizing exogenous or endogenous lipids. J Gen Microbiol 134:2907–2915
Iida T, Sumita T, Ohta A, Takagi M (2000) The cytochrome p450alk multigene family of an n-alkane-assimilating yeast, Yarrowia lipolytica: cloning and characterization of genes coding for new cyp52 family members. Yeast 16:1077–1087
Jacquier N, Schneiter R (2010) Ypk1, the yeast orthologue of the human serum- and glucocorticoid-induced kinase, is required for efficient uptake of fatty acids. J Cell Sci 123:2218–2227
Kihara A, Sakuraba H, Ikeda M, Denpoh A, Igarashi Y (2008) Membrane topology and essential amino acid residues of Phs1, a 3-hydroxyl-CoA dehydratase involved in very long-chain fatty acid elongation. J Biol Chem 283:11199–11209
Koffel R, Tiwari R, Falquet L, Schneiter R (2005) The Saccharomyces cerevisiae YLL012/YEH1, YLR020/YEH2, and TGL1 genes encode a novel family of membrane-anchored lipases that are required for steryl ester hydrolysis. Mol Cell Biol 25:1655–1668
Kohlwein SD (2010) Triacylglycerol homeostasis: insights from yeast. J Biol Chem 285(21):15663–15667
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 21:109–125
Kurat CF, Natter K, Petschnigg J, Wolinski H, Scheuringer K, Scholz H, Zimmermann R, Leber R, Zechner R, Kohlwein SD (2006) Obese yeast: triglyceride lipolysis is functionally conserved from mammals to yeast. J Biol Chem 281:491–500
Luo YS, Nicaud JM, Van Veldhoven PP, Chardot T (2002) The acyl-CoA oxidases from the yeast Yarrowia lipolytica: characterization of aox2p. Arch Biochem Biophys 407:32–38
Meng X, Jianming Y, Xin X, Lei Z, Qingjuan N, Mo X (2009) Biodiesel production from oleaginous microorganisms. Renewable Energy 34:1–5
Mlickova K, Luo Y, D'Andrea S, Pec P, Chardot T, Nicaud J (2004a) Acyl-CoA oxidase, a key step for lipid accumulation in the yeast Yarrowia lipolytica. J Mol Catal B Enzym 28:81–85
Mlickova K, Roux E, Athenstaedt K, d'Andrea S, Daum G, Chardot T, Nicaud JM (2004b) Lipid accumulation, lipid body formation, and acyl coenzyme a oxidases of the yeast Yarrowia lipolytica. Appl Environ Microbiol 70:3918–3924
Mullner H, Deutsh G, Leitner E, Ingolic E (2005) YEH2/YLR020c encodes a novel steryl ester hydrolase of the yeast Saccharomyces cerevisiae. J Biol Chem 280:13321–13328
Nielsen J (2009) Systems biology of lipid metabolism: from yeast to human. FEBS Lett 583:3905–3913
Picataggio S, Rohrer T, Deanda K, Lanning D, Reynolds R, Mielenz J, Eirich LD (1992) Metabolic engineering of Candida tropicalis for the production of long-chain dicarboxylic acids. Nat Biotechnol (N Y) 10:894–898
Pignede G, Wang H, Fudalej F, Gaillardin C, Seman M, Nicaud JM (2000) Characterization of an extracellular lipase encoded by lip2 in Yarrowia lipolytica. J Bacteriol 182:2802–2810
Poirier Y, Erard N, Petetot JM (2001) Synthesis of polyhydroxyalkanoate in the peroxisome of Saccharomyces cerevisiae by using intermediates of fatty acid beta-oxidation. Appl Environ Microbiol 67:5254–5260
Poirier Y, Erard N, MacDonald-Comber PJ (2002) Synthesis of polyhydroxyalkanoate in the peroxisome of Pichia pastoris. FEMS Microbiol Lett 207:97–102
Rajakumari S, Grillitsch K, Daum G (2008) Synthesis and turnover of non-polar lipids in yeast. Prog Lipid Res 47:157–171
Ratledge C (1989) Microbial lipids, vol 2. Academic, London
Ratledge C (1994) Yeasts, moulds, algae and bacteria as sources of lipids. In: Kamel BS, Kakuda Y (eds) Technological advances in improved and alternative sources of lipids. Blackie Academic and Professional, London, pp 235–291
Ratledge C (2001) Structure and modified lipids. Marcel Dekker, New York
Ratledge C (2004) Fatty acid biosynthesis in microorganisms being used for single cell oil production. Biochimie 86:807–815
Ratledge C, Wynn JP (2002) The biochemistry and molecular biology of lipid accumulation in oleaginous microorganisms. Adv Appl Microbiol 51:1–51
Ratlege C, Tan K (1990) Oils and fats: production, degradation and utilization by yeasts. In: Verachtert H, De Mot R (eds) Yeast biotechnology and biocatalysis. Marcel Dekker, New York, pp 223–254
Rattray JBM (1988) Microbial lipids, vol 1. Academic, London
Ruenwai R, Cheevadhanarak S, Laoteng K (2009) Overexpression of acetyl-CoA carboxylase gene of Mucor rouxii enhanced fatty acid content in Hansenula polymorpha. Mol Biotechnol 42:327–332
Sabirova J, Haddouche R, Van Bogaert I, Mulaa F, Verstraete W, Timmis K, Schmidt-Dannert C, Nicaud JM, Soetaert W (2010) The lipoyeasts project: using the oleaginous yeast Y. lipolytica in combination with specific bacterial genes for the bioconversion of lipids, fats and oils into high value products. Microb Biotechnol 4:47–54
Sandager L, Gustavsson MH, Stahl U, Dahlqvist A, Wiberg E, Banas A, Lenman M, Ronne H, Stymne S (2002) Storage lipid synthesis is non-essential in yeast. J Biol Chem 277:6478–6482
Schmidt-Dannert C (2000) Engineering novel carotenoids in microorganisms. Curr Opin Biotechnol 11:255–261
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 68:501–517
Shen YQ, Burger G (2009) Plasticity of a key metabolic pathway in fungi. Funct Integr Genomics 9:145–151
Shen YQ, Lang BF, Burger G (2009) Diversity and dispersal of a ubiquitous protein family: acyl-CoA dehydrogenases. Nucleic Acids Res 37:5619–5631
Steen EJ, Kang Y, Bokinsky G, Hu Z, Schirmer A, McClure A, Del Cardayre SB, Keasling JD (2010) Microbial production of fatty-acid-derived fuels and chemicals from plant biomass. Nature 463:559–562
Strijbis K, Distel B (2010) Intracellular acetyl unit transport in fungal carbon metabolism. Eukaryot Cell 9:1809–1815
Strijbis K, van Roermund CW, Hardy GP, van den Burg J, Bloem K, de Haan J, van Vlies N, Wanders RJ, Vaz FM, Distel B (2009) Identification and characterization of a complete carnitine biosynthesis pathway in Candida albicans. FASEB J 23:2349–2359
Swartzman EE, Viswanathan MN, Thorner J (1996) The pal1 gene product is a peroxisomal atp-binding cassette transporter in the yeast Saccharomyces cerevisiae. J Cell Biol 132:549–563
Tang W, Zhang S, Tan H, Zhao ZK (2010) Molecular cloning and characterization of a malic enzyme gene from the oleaginous yeast Lipomyces starkeyi. Mol Biotechnol 45:121–128
Tehlivets O, Scheuringer K, Kohlwein SD (2007) Fatty acid synthesis and elongation in yeast. Biochim Biophys Acta 1771:255–270
Theodoulou FL, Holdsworth M, Baker A (2006) Peroxisomal abc transporters. FEBS Lett 580:1139–1155
Thevenieau F (2006) Metabolic engineering of the yeast Yarrowia lipolytica for the production of long-chain dicarboxylic acids from renewable oil feedstock. Ph.D. thesis
Thevenieau F, Le Dall MT, Nthangeni B, Mauersberger S, Marchal R, Nicaud JM (2007) Characterization of Yarrowia lipolytica mutants affected in hydrophobic substrate utilization. Fungal Genet Biol 44:531–542
Thevenieau F, Beopoulos A, Desfougeres T, Sabirova J, Albertin K, Zinjarde S, Nicaud JM (2009) Uptake and assimilation of hydrophobic substrates by the oleaginous yeast Yarrowia lipolytica. In: Timmis KN (ed) Handbook of hydrocarbon and lipid microbiology. Springer, Berlin
Thurmond W (2008) Biodiesel 2020: a global market survey. Emerging markets
Visser H, van Ooyen AJ, Verdoes JC (2003) Metabolic engineering of the astaxanthin-biosynthetic pathway of Xanthophyllomyces dendrorhous. FEMS Yeast Res 4:221–231
Wache Y, Aguedo M, Nicaud JM, Belin JM (2003) Catabolism of hydroxyacids and biotechnological production of lactones by Yarrowia lipolytica. Appl Microbiol Biotechnol 61:393–404
Wang H, Le Clainche A, Le Dall MT, Wache Y, Pagot Y, Belin JM, Gaillardin C, Nicaud JM (1998) Cloning and characterization of the peroxisomal acyl CoA oxidase aco3 gene from the alkane-utilizing yeast Yarrowia lipolytica. Yeast 14:1373–1386
Wang H, Le Dall MT, Wache Y, Laroche C, Belin JM, Nicaud JM (1999) Cloning, sequencing, and characterization of five genes coding for acyl-CoA oxidase isozymes in the yeast Yarrowia lipolytica. Cell Biochem Biophys 31:165–174
Wynn JP, Kendrick A, Ratledge C (1997) Sesamol as an inhibitor of growth and lipid metabolism in Mucor circinelloides via its action on malic enzyme. Lipids 32:605–610
Yamagami S, Iida T, Nagata Y, Ohta A, Takagi M (2001) Isolation and characterization of acetoacetyl-CoA thiolase gene essential for n-decane assimilation in yeast Yarrowia lipolytica. Biochem Biophys Res Commun 28:832–838
Yen CL, Stone SJ, Koliwad S, Harris C, Farese RV Jr (2008) Thematic review series: glycerolipids. Dgat enzymes and triacylglycerol biosynthesis. J Lipid Res 49:2283–2301
Ykema A, Verbree EC, van Verseveld HW, Smit H (1986) Mathematical modelling of lipid production by oleaginous yeasts in continuous cultures. Antonie Leeuwenhoek 52:491–506
Zhang Y, Adams IP, Ratledge C (2007) Malic enzyme: the controlling activity for lipid production? Overexpression of malic enzyme in Mucor circinelloides leads to a 2.5-fold increase in lipid accumulation. Microbiology 153:2013–2025
Zou Z, DiRusso CC, Ctrnacta V, Black PN (2002) Fatty acid transport in Saccharomyces cerevisiae. Directed mutagenesis of FAT1 distinguishes the biochemical activities associated with Fat1p. J Biol Chem 277:31062–31071
Zweytick D, Athenstaedt K, Daum G (2000) Intracellular lipid particles of eukaryotic cells. Biochim Biophys Acta 1469:101–120
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Beopoulos, A., Nicaud, JM. & Gaillardin, C. An overview of lipid metabolism in yeasts and its impact on biotechnological processes. Appl Microbiol Biotechnol 90, 1193–1206 (2011). https://doi.org/10.1007/s00253-011-3212-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00253-011-3212-8