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Lipid metabolism of the oleaginous yeast Lipomyces starkeyi

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Abstract

The oleaginous yeast Lipomyces starkeyi is an excellent sustainable lipid producer, which can convert industrial wastes into lipids and accumulate triacylglycerols (TAG) by > 70% of its dry cell weight. Recent studies using omics technologies applied in L. starkeyi have aided in obtaining greater understanding of the important mechanisms of lipid metabolism in L. starkeyi. Therefore, the development of genetic engineering tools for L. starkeyi has led to accelerated efforts for a highly efficient production of lipids.

This review focuses on the aspects of TAG and fatty acid synthesis pathways in L. starkeyi. We also present a quite effective strategy to obtain L. starkeyi mutants accumulating a larger amount of lipids and having a higher lipid production rate than the wild-type strain. The analysis of these mutants exhibiting high lipid production has led to the identification of important genes for achieving highly effective lipid production and thus advanced improvement in lipid production. Herein, our aim was to provide useful information to advance the development of L. starkeyi as a cost-effective TAG feedstock.

Key Points

•Oleaginous yeast Lipomyces starkeyi is an excellent sustainable lipid producer.

•Efficient isolation of lipid-enriched L. starkeyi mutants depends on the low density of lipids.

•Increased acyl-CoA synthesis pathway is important for improving lipid productivity.

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References

  • Angerbauer C, Siebenhofer M, Mittelbach M, Guebitz GM (2008) Conversion of sewage sludge into lipids by Lipomyces starkeyi for biodiesel production. Bioresour Technol 99(8):3051–3056. https://doi.org/10.1016/j.biortech.2007.06.045

    Article  CAS  PubMed  Google Scholar 

  • Beligon V, Christophe G, Fontanille P, Larroche C (2016) Microbial lipids as potential source to food supplements. Curr Opin Food Sci 7:35–42

    Google Scholar 

  • Brandenburg J, Blomqvist J, Pickova J, Bonturi N, Sandgren M, Passoth V (2016) Lipid production from hemicellulose with Lipomyces starkeyi in a pH regulated fed-batch cultivation. Yeast 33(8):451–462

    CAS  PubMed  Google Scholar 

  • Brandenburg J, Poppele I, Blomqvist J, Puke M, Pickova J, Sandgren M, Rapoport A, Vedernikovs N, Passoth V (2018) Bioethanol and lipid production from the enzymatic hydrolysate of wheat straw after furfural extraction. Appl Microbiol Biotechnol 102(14):6269–6277

    CAS  PubMed  PubMed Central  Google Scholar 

  • Buček A, Matoušková P, Sychrova H, Pichová I, Hrušková-Heidingsfeldová O (2014) Δ12-Fatty acid desaturase from Candida parapsilosis is a multifunctional desaturase producing a range of polyunsaturated and hydroxylated fatty acids. PLoS One 9(3):e93322

    PubMed  PubMed Central  Google Scholar 

  • Calvey CH, Willis LB, Jeffries TW (2014) An optimized transformation protocol for Lipomyces starkeyi. Curr Genet 60(3):223–230

    CAS  PubMed  Google Scholar 

  • Chapman KD, Dyer JM, Mullen RT (2012) Biogenesis and functions of lipid droplets in plants thematic review series: lipid droplet synthesis and metabolism: from yeast to man. J Lipid Res 53(2):215–226

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dai Z, Deng S, Culley DE, Bruno KS, Magnuson JK (2017) Agrobacterium tumefaciens-mediated transformation of oleaginous yeast Lipomyces species. Appl Microbiol Biotechnol 101(15):6099–6110

    CAS  PubMed  Google Scholar 

  • Damude HG, Zhang H, Farrall L, Ripp KG, Tomb J-F, Hollerbach D, Yadav NS (2006) Identification of bifunctional Δ12/ω3 fatty acid desaturases for improving the ratio of ω3 to ω6 fatty acids in microbes and plants. Proc Natl Acad Sci 103(25):9446–9451

    CAS  PubMed  Google Scholar 

  • Deinema MH, Landheer C (1956) Composition of fats, produced by lipomyces starkeyi, under various conditions. Arch Mikrobiol 25(2):193–200

    CAS  PubMed  Google Scholar 

  • Fakas S (2017) Lipid biosynthesis in yeasts: a comparison of the lipid biosynthetic pathway between the model nonoleaginous yeast Saccharomyces cerevisiae and the model oleaginous yeast Yarrowia lipolytica. Eng Life Sci 17(3):292–302

    CAS  PubMed  Google Scholar 

  • Flikweert MT, van der Zanden L, Janssen WMTM, Yde Steensma H, van Dijken JP, Pronk JT (1996) Pyruvate decarboxylase: an indispensable enzyme for growth of Saccharomyces cerevisiae on glucose. Yeast 12(3):247–257

    CAS  PubMed  Google Scholar 

  • Heath RJ, White SW, Rock CO (2001) Lipid biosynthesis as a target for antibacterial agents. Prog Lipid Res 40(6):467–497. https://doi.org/10.1016/s0163-7827(01)00012-1

    Article  CAS  PubMed  Google Scholar 

  • Henry SA, Kohlwein SD, Carman GM (2012) Metabolism and regulation of glycerolipids in the yeast Saccharomyces cerevisiae. Genetics 190(2):317–349

    CAS  PubMed  PubMed Central  Google Scholar 

  • Juanssilfero AB, Kahar P, Amza RL, Miyamoto N, Otsuka H, Matsumoto H, Kihira C, Thontowi A, Ogino C, Prasetya B (2018) Effect of inoculum size on single-cell oil production from glucose and xylose using oleaginous yeast Lipomyces starkeyi. J Biosci Bioeng 125(6):695–702

    CAS  PubMed  Google Scholar 

  • Juanssilfero AB, Kahar P, Amza RL, Sudesh K, Ogino C, Prasetya B, Kondo A (2019) Lipid production by Lipomyces starkeyi using sap squeezed from felled old oil palm trunks. J Biosci Bioeng 127(6):726–731

    CAS  PubMed  Google Scholar 

  • Katre G, Ajmera N, Zinjarde S, RaviKumar A (2017) Mutants of Yarrowia lipolytica NCIM 3589 grown on waste cooking oil as a biofactory for biodiesel production. Microb Cell Factories 16(1):176. https://doi.org/10.1186/s12934-017-0790-x

    Article  CAS  Google Scholar 

  • Kobayashi SD, Nagiec MM (2003) Ceramide/long-chain base phosphate rheostat in Saccharomyces cerevisiae: regulation of ceramide synthesis by Elo3p and Cka2p. Eukaryot Cell 2(2):284–294

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kosa M, Ragauskas AJ (2011) Lipids from heterotrophic microbes: advances in metabolism research. Trends Biotechnol 29(2):53–61. https://doi.org/10.1016/j.tibtech.2010.11.002

    Article  CAS  PubMed  Google Scholar 

  • Kurtzman CP, Fell JW, Boekhout T, Robert V (2011) Methods for isolation, phenotypic characterization and maintenance of yeasts The yeasts. Elsevier, pp 87-110

  • Lazar Z, Liu N, Stephanopoulos G (2018) Holistic approaches in lipid production by Yarrowia lipolytica. Trends Biotechnol 36(11):1157–1170

    CAS  PubMed  Google Scholar 

  • Ledesma-Amaro R, Nicaud J-M (2016) Yarrowia lipolytica as a biotechnological chassis to produce usual and unusual fatty acids. Prog Lipid Res 61:40–50

    CAS  PubMed  Google Scholar 

  • Li Q, Du W, Liu D (2008) Perspectives of microbial oils for biodiesel production. Appl Microbiol Biotechnol 80(5):749–756

    CAS  PubMed  Google Scholar 

  • Lomascolo A, Dubreucq E, Galzy P (1996) Study of the Δ12-desaturase system of Lipomyces starkeyi. Lipids 31(3):253–259

    CAS  PubMed  Google Scholar 

  • Martin CE, Oh C-S, Jiang Y (2007) Regulation of long chain unsaturated fatty acid synthesis in yeast. Biochim Biophys Acta 1771(3):271–285

    CAS  PubMed  Google Scholar 

  • Maruyama Y, Toya Y, Kurokawa H, Fukano Y, Sato A, Umemura H, Yamada K, Iwasaki H, Tobori N, Shimizu H (2018) Characterization of oil-producing yeast Lipomyces starkeyi on glycerol carbon source based on metabolomics and 13 C-labeling. Appl Microbiol Biotechnol 102(20):8909–8920

    CAS  PubMed  Google Scholar 

  • Matsuzawa T, Maehara T, Kamisaka Y, Ara S, Takaku H, Yaoi K (2018) Identification and characterization of Δ12 and Δ12/Δ15 bifunctional fatty acid desaturases in the oleaginous yeast Lipomyces starkeyi. Appl Microbiol Biotechnol 102(20):8817–8826

    CAS  PubMed  Google Scholar 

  • Matsuzawa T, Kamisaka Y, Maehara T, Takaku H, Yaoi K (2020) Identification and characterization of two fatty acid elongases in Lipomyces starkeyi. Appl Microbiol Biotechnol 104(6):2537–2544

    CAS  PubMed  Google Scholar 

  • Muniraj IK, Uthandi SK, Hu Z, Xiao L, Zhan X (2015) Microbial lipid production from renewable and waste materials for second-generation biodiesel feedstock. Environ Technol Rev 4(1):1–16

    CAS  Google Scholar 

  • Oguri E, Masaki K, Naganuma T, Iefuji H (2012) Phylogenetic and biochemical characterization of the oil-producing yeast Lipomyces starkeyi. Antonie Van Leeuwenhoek 101(2):359–368

    CAS  PubMed  Google Scholar 

  • Oguro Y, Yamazaki H, Shida Y, Ogasawara W, Takagi M, Takaku H (2015) Multicopy integration and expression of heterologous genes in the oleaginous yeast, Lipomyces starkeyi. Biosci Biotechnol Biochem 79(3):512–515

    CAS  PubMed  Google Scholar 

  • Oguro Y, Yamazaki H, Ara S, Shida Y, Ogasawara W, Takagi M, Takaku H (2017) Efficient gene targeting in non-homologous end-joining-deficient Lipomyces starkeyi strains. Curr Genet 63(4):751–763

    CAS  PubMed  Google Scholar 

  • Oh C-S, 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

    CAS  PubMed  Google Scholar 

  • Ohno Y, Suto S, Yamanaka M, Mizutani Y, Mitsutake S, Igarashi Y, Sassa T, Kihara A (2010) ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis. Proc Natl Acad Sci 107(43):18439–18444

    CAS  PubMed  Google Scholar 

  • Papanikolaou S, Aggelis G (2011) Lipids of oleaginous yeasts. Part I: Biochemistry of single cell oil production. Eur J Lipid Sci Technol 113(8):1031–1051. https://doi.org/10.1002/ejlt.201100014

    Article  CAS  Google Scholar 

  • Park Y-K, Nicaud J-M, Ledesma-Amaro R (2018) The engineering potential of Rhodosporidium toruloides as a workhorse for biotechnological applications. Trends Biotechnol 36(3):304–317

    CAS  PubMed  Google Scholar 

  • Pomraning KR, Collett JR, Kim J, Panisko EA, Culley DE, Dai Z, Deng S, Hofstad BA, Butcher MG, Magnuson JK (2019) Transcriptomic analysis of the oleaginous yeast Lipomyces starkeyi during lipid accumulation on enzymatically treated corn stover hydrolysate. Biotechnol Biofuels 12(1):162

    PubMed  PubMed Central  Google Scholar 

  • Ratledge C (2014) The role of malic enzyme as the provider of NADPH in oleaginous microorganisms: a reappraisal and unsolved problems. Biotechnol Lett 36(8):1557–1568

    CAS  PubMed  Google Scholar 

  • Ratledge C, Wynn JP (2002) The biochemistry and molecular biology of lipid accumulation in oleaginous microorganisms. Adv Appl Microbiol 51:1–52

    CAS  PubMed  Google Scholar 

  • Riley R, Haridas S, Wolfe KH, Lopes MR, Hittinger CT, Göker M, Salamov AA, Wisecaver JH, Long TM, Calvey CH (2016) Comparative genomics of biotechnologically important yeasts. Proc Natl Acad Sci 113(35):9882–9887

    CAS  PubMed  Google Scholar 

  • Rössler H, Rieck C, Delong T, Hoja U, Schweizer E (2003) Functional differentiation and selective inactivation of multiple Saccharomyces cerevisiae genes involved in very-long-chain fatty acid synthesis. Mol Gen Genomics 269(2):290–298

    Google Scholar 

  • 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

    CAS  PubMed  PubMed Central  Google Scholar 

  • Signori L, Ami D, Posteri R, Giuzzi A, Mereghetti P, Porro D, Branduardi P (2016) Assessing an effective feeding strategy to optimize crude glycerol utilization as sustainable carbon source for lipid accumulation in oleaginous yeasts. Microb Cell Factories 15(1):75

    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(28):16537–16544

    CAS  PubMed  Google Scholar 

  • Sutanto S, Zullaikah S, Tran-Nguyen PL, Ismadji S, Ju Y-H (2018) Lipomyces starkeyi: its current status as a potential oil producer. Fuel Process Technol 177:39–55

    CAS  Google Scholar 

  • Taheripour F, Hertel TW, Ramankutty N (2019) Market-mediated responses confound policies to limit deforestation from oil palm expansion in Malaysia and Indonesia. Proc Natl Acad Sci 116(38):19193–19199

    CAS  PubMed  Google Scholar 

  • Tai M, Stephanopoulos G (2013) Engineering the push and pull of lipid biosynthesis in oleaginous yeast Yarrowia lipolytica for biofuel production. Metab Eng 15:1–9

    CAS  PubMed  Google Scholar 

  • Takaku H, Miyajima A, Kazama H, Sato R, Ara S, Matsuzawa T, Yaoi K, Araki H, Shida Y, Ogasawara W (2020) A novel electroporation procedure for highly efficient transformation of Lipomyces starkeyi. J Microbiol Methods 169:105816

    CAS  PubMed  Google Scholar 

  • Tang W, Zhang S, Wang Q, Tan H, Zhao ZK (2009) The isocitrate dehydrogenase gene of oleaginous yeast Lipomyces starkeyi is linked to lipid accumulation. Can J Microbiol 55(9):1062–1069

    CAS  PubMed  Google Scholar 

  • 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(2):121–128

    CAS  PubMed  Google Scholar 

  • Tapia VE, Anschau A, Coradini AL, Franco TT, Deckmann AC (2012) Optimization of lipid production by the oleaginous yeast Lipomyces starkeyi by random mutagenesis coupled to cerulenin screening. AMB Express 2(1):64–64. https://doi.org/10.1186/2191-0855-2-64

    Article  CAS  Google Scholar 

  • Tehlivets O, Scheuringer K, Kohlwein SD (2007) Fatty acid synthesis and elongation in yeast. Biochim Biophys Acta 1771(3):255–270

    CAS  PubMed  Google Scholar 

  • Tkachenko A, Tigunova O, Shulga S (2013) Microbial lipids as a source of biofuel. Cytol Genet 47(6):343–348

    Google Scholar 

  • Toke DA, Martin CE (1996) Isolation and characterization of a gene affecting fatty acid elongation in Saccharomyces cerevisiae. J Biol Chem 271(31):18413–18422

    CAS  PubMed  Google Scholar 

  • Vasconcelos B, Teixeira JC, Dragone G, Teixeira JA (2019) Oleaginous yeasts for sustainable lipid production—from biodiesel to surf boards, a wide range of “green” applications. Appl Microbiol Biotechnol 103(9):3651–3667

    CAS  PubMed  Google Scholar 

  • Wang J, Li R, Lu D, Ma S, Yan Y, Li W (2009) A quick isolation method for mutants with high lipid yield in oleaginous yeast. World J Microbiol Biotechnol 25(5):921–925. https://doi.org/10.1007/s11274-009-9960-2

    Article  CAS  Google Scholar 

  • Wang R, Wang J, Xu R, Fang Z, Liu A (2014) Oil production by the oleaginous yeast Lipomyces starkeyi using diverse carbon sources. BioResources 9(4):7027–7040

    Google Scholar 

  • Wei DS, Li MC, Zhang X, Zhou H, Xing L (2006) A novel Delta12-fatty acid desaturase gene from methylotrophic yeast Pichia pastoris GS115. Acta Biochim Pol 53(4):753–759

    CAS  PubMed  Google Scholar 

  • Xue Z, Sharpe PL, Hong S-P, 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

    CAS  PubMed  Google Scholar 

  • Yamada R, Kashihara T, Ogino H (2017a) Improvement of lipid production by the oleaginous yeast Rhodosporidium toruloides through UV mutagenesis. World J Microbiol Biotechnol 33(5):99–99. https://doi.org/10.1007/s11274-017-2269-7

    Article  CAS  PubMed  Google Scholar 

  • Yamada R, Yamauchi A, Kashihara T, Ogino H (2017b) Evaluation of lipid production from xylose and glucose/xylose mixed sugar in various oleaginous yeasts and improvement of lipid production by UV mutagenesis. Biochem Eng J 128:76–82. https://doi.org/10.1016/j.bej.2017.09.010

    Article  CAS  Google Scholar 

  • Yamazaki H, Kobayashi S, Ebina S, Abe S, Ara S, Shida Y, Ogasawara W, Yaoi K, Araki H, Takaku H (2019) Highly selective isolation and characterization of Lipomyces starkeyi mutants with increased production of triacylglycerol. Appl Microbiol Biotechnol 103(15):6297–6308. https://doi.org/10.1007/s00253-019-09936-3

    Article  CAS  PubMed  Google Scholar 

  • Zhu Z, Zhang S, Liu H, Shen H, Lin X, Yang F, Zhou YJ, Jin G, Ye M, Zou H (2012) A multi-omic map of the lipid-producing yeast Rhodosporidium toruloides. Nat Commun 3(1):1–12

    Google Scholar 

  • Zimmermann C, Santos A, Gable K, Epstein S, Gururaj C, Chymkowitch P, Pultz D, Rødkær SV, Clay L, Bjørås M (2013) TORC1 inhibits GSK3-mediated Elo2 phosphorylation to regulate very long chain fatty acid synthesis and autophagy. Cell Rep 5(4):1036–1046

    CAS  PubMed  Google Scholar 

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Funding

This study was supported in part by a grant of the Science and Technology Research Promotion Program for Agriculture, Forestry, Fisheries and Food Industry, a grant of the Development of Production Techniques for Highly Functional Biomaterials Using Smart Cells of Plants and Other Organisms, and a grant from JSPS KAKENHI (Grant Number 18 K05401).

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Authors and Affiliations

  1. Department of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, 265-1 Higashijima, Akiha-ku, Niigata, 956-8603, Japan

    Hiroaki Takaku & Harutake Yamazaki

  2. Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8566, Japan

    Tomohiko Matsuzawa & Katsuro Yaoi

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  1. Hiroaki Takaku
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  2. Tomohiko Matsuzawa
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  4. Harutake Yamazaki
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HT conceived the manuscript topics and designed the structure of this review. HT, TM, and HY wrote the manuscript. KY helped in data collection and in manuscript editing. All authors read and approved the manuscript.

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Correspondence to Hiroaki Takaku.

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Takaku, H., Matsuzawa, T., Yaoi, K. et al. Lipid metabolism of the oleaginous yeast Lipomyces starkeyi. Appl Microbiol Biotechnol 104, 6141–6148 (2020). https://doi.org/10.1007/s00253-020-10695-9

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  • DOI: https://doi.org/10.1007/s00253-020-10695-9

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