Reconstruction of genome-scale metabolic model of Yarrowia lipolytica and its application in overproduction of triacylglycerol

Songsong Wei , Xingxing Jian , Jun Chen , Cheng Zhang , Qiang Hua

Bioresources and Bioprocessing ›› 2017, Vol. 4 ›› Issue (1) : 51

PDF
Bioresources and Bioprocessing ›› 2017, Vol. 4 ›› Issue (1) : 51 DOI: 10.1186/s40643-017-0180-6
Research

Reconstruction of genome-scale metabolic model of Yarrowia lipolytica and its application in overproduction of triacylglycerol

Author information +
History +
PDF

Abstract

Background

Yarrowia lipolytica is widely studied as a non-conventional model yeast owing to the high level of lipid accumulation. Therein, triacylglycerol (TAG) is a major component of liposome. In order to investigate the TAG biosynthesis mechanism at a systematic level, a novel genome-scale metabolic model of Y. lipolytica was reconstructed based on a previous model iYL619_PCP published by our lab and another model iYali4 published by Kerkhoven et al.

Results

The novel model iYL_2.0 contains 645 genes, 1083 metabolites, and 1471 reactions, which was validated more effective on simulations of specific growth rate. The precision of 29 carbon sources utilities reached up to 96.6% when simulated by iYL_2.0. In minimal growth medium, 111 genes were identified as essential for cell growth, whereas 66 essential genes were identified in yeast extract medium, which were verified by database of essential genes, suggesting a better prediction ability of iYL_2.0 in comparison with other existing models. In addition, potential metabolic engineering targets of improving TAG production were predicted by three in silico methods developed in-house, and the effects of amino acids supplementation were investigated based on model iYL_2.0.

Conclusions

The reconstructed model iYL_2.0 is a powerful platform for efficiently optimizing the metabolism of TAG and systematically understanding the physiological mechanism of Y. lipolytica.

Keywords

Yarrowia lipolytica / Genome-scale metabolic model / iYL_2.0 / Triacylglycerol / Gene-level prediction targets

Cite this article

Download citation ▾
Songsong Wei, Xingxing Jian, Jun Chen, Cheng Zhang, Qiang Hua. Reconstruction of genome-scale metabolic model of Yarrowia lipolytica and its application in overproduction of triacylglycerol. Bioresources and Bioprocessing, 2017, 4(1): 51 DOI:10.1186/s40643-017-0180-6

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Apweiler R, Bairoch A, Wu CH, Barker WC, Boeckmann B, Ferro S, Gasteiger E, Huang H, Lopez R, Magrane M, . UniProt: the universal protein knowledgebase. Nucleic Acids Res, 2004, 32: D115-D119.

[2]

Athenstaedt K. YALI0E32769g (DGA1) and YALI0E16797g (LRO1) encode major triacylglycerol synthases of the oleaginous yeast Yarrowia lipolytica. Biochem Biophys Acta, 2011, 1811: 587-596.

[3]

Beopoulos A, Nicaud JM, Gaillardin C. An overview of lipid metabolism in yeasts and its impact on biotechnological processes. Appl Microbiol Biotechnol, 2011, 90: 1193-1206.

[4]

Blazeck J, Hill A, Liu LQ, Knight R, Miller J, Pan A, Otoupal P, Alper HS. Harnessing Yarrowia lipolytica lipogenesis to create a platform for lipid and biofuel production. Nat Commun, 2014, 5: 3131.

[5]

Burgard AP, Pharkya P, Maranas CD. Optknock: a bilevel programming framework for identifying gene knockout strategies for microbial strain optimization. Biotechnol Bioeng, 2003, 84: 647-657.

[6]

Degtyarenko K, de Matos P, Ennis M, Hastings J, Zbinden M, McNaught A, Alcantara R, Darsow M, Guedj M, Ashburner M. ChEBI: a database and ontology for chemical entities of biological interest. Nucleic Acids Res, 2008, 36: D344-D350.

[7]

Dulermo T, Nicaud JM. Involvement of the G3P shuttle and beta-oxidation pathway in the control of TAG synthesis and lipid accumulation in Yarrowia lipolytica. Metab Eng, 2011, 13: 482-491.

[8]

Feist AM, Herrgard MJ, Thiele I, Reed JL, Palsson BO. Reconstruction of biochemical networks in microorganisms. Nat Rev Microbiol, 2009, 7: 129-143.

[9]

Forster A, Aurich A, Mauersberger S, Barth G. Citric acid production from sucrose using a recombinant strain of the yeast Yarrowia lipolytica. Appl Microbiol Biotechnol, 2007, 75: 1409-1417.

[10]

Gao F, Luo H, Zhang CT, Zhang R. Gene essentiality analysis based on DEG 10, an updated database of essential genes. Methods Mol Biol, 2015, 1279: 219-233.

[11]

Giaever G, Chu AM, Ni L, Connelly C, Riles L, Veronneau S, Dow S, Lucau-Danila A, Anderson K, Andre B, . Functional profiling of the Saccharomyces cerevisiae genome. Nature, 2002, 418: 387-391.

[12]

Gu D, Zhang C, Zhou S, Wei L, Hua Q. IdealKnock: a framework for efficiently identifying knockout strategies leading to targeted overproduction. Comput Biol Chem, 2016, 61: 229-237.

[13]

Heavner BD, Smallbone K, Barker B, Mendes P, Walker LP. Yeast 5—an expanded reconstruction of the Saccharomyces cerevisiae metabolic network. BMC Syst Biol, 2012, 6: 55.

[14]

Herrgard MJ, Swainston N, Dobson P, Dunn WB, Arga KY, Arvas M, Bluthgen N, Borger S, Costenoble R, Heinemann M, . A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology. Nat Biotechnol, 2008, 26: 1155-1160.

[15]

Jian X, Li N, Zhang C, Hua Q. In silico profiling of cell growth and succinate production in Escherichia coli NZN111. Bioresour Bioprocess, 2016, 3: 48.

[16]

Jian X, Zhou S, Zhang C, Hua Q. In silico identification of gene amplification targets based on analysis of production and growth coupling. Bio Syst, 2016, 145: 1-8.

[17]

Kanehisa M, Araki M, Goto S, Hattori M, Hirakawa M, Itoh M, Katayama T, Kawashima S, Okuda S, Tokimatsu T, . KEGG for linking genomes to life and the environment. Nucleic Acids Res, 2008, 36: D480-D484.

[18]

Kennedy EP. Metabolism of lipides. Annu Rev Biochem, 1957, 26: 119-148.

[19]

Kerkhoven EJ, Pomraning KR, Baker SE, Nielsen J. Regulation of amino-acid metabolism controls flux to lipid accumulation in Yarrowia lipolytica. NPJ Syst Biol Appl, 2016, 2: 16005.

[20]

Lanciotti R, Gianotti A, Baldi D, Angrisani R, Suzzi G, Mastrocola D, Guerzoni ME. Use of Yarrowia lipolytica strains for the treatment of olive mill wastewater. Bioresour Technol, 2005, 96: 317-322.

[21]

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

[22]

Loira N, Dulermo T, Nicaud JM, Sherman DJ. A genome-scale metabolic model of the lipid-accumulating yeast Yarrowia lipolytica. BMC Syst Biol, 2012, 6: 35.

[23]

Makri A, Fakas S, Aggelis G. Metabolic activities of biotechnological interest in Yarrowia lipolytica grown on glycerol in repeated batch cultures. Bioresour Technol, 2010, 101: 2351-2358.

[24]

Morin N, Cescut J, Beopoulos A, Lelandais G, Le Berre V, Uribelarrea JL, Molina-Jouve C, Nicaud JM. Transcriptomic analyses during the transition from biomass production to lipid accumulation in the oleaginous yeast Yarrowia lipolytica. PLoS ONE, 2011, 6: e27966.

[25]

Oberhardt MA, Palsson BO, Papin JA. Applications of genome-scale metabolic reconstructions. Mol Syst Biol, 2009, 5: 320.

[26]

Orth JD, Thiele I, Palsson BO. What is flux balance analysis?. Nat Biotechnol, 2010, 28: 245-248.

[27]

Pan P, Hua Q. Reconstruction and in silico analysis of metabolic network for an oleaginous yeast, Yarrowia lipolytica. PloS ONE, 2012, 7: e51535.

[28]

Papanikolaou S, Aggelis G. Lipid production by Yarrowia lipolytica growing on industrial glycerol in a single-stage continuous culture. Bioresour Technol, 2002, 82: 43-49.

[29]

Papanikolaou S, Aggelis G. Yarrowia lipolytica: a model microorganism used for the production of tailor-made lipids. Eur J Lipid Sci Technol, 2010, 112: 639-654.

[30]

Papanikolaou S, Chevalot I, Komaitis M, Marc I, Aggelis G. Single cell oil production by Yarrowia lipolytica growing on an industrial derivative of animal fat in batch cultures. Appl Microbiol Biotechnol, 2002, 58: 308-312.

[31]

Qiao K, Imam Abidi SH, Liu H, Zhang H, Chakraborty S, Watson N, Kumaran Ajikumar P, Stephanopoulos G. Engineering lipid overproduction in the oleaginous yeast Yarrowia lipolytica. Metab Eng, 2015, 29: 56-65.

[32]

Satish Kumar V, Dasika MS, Maranas CD. Optimization based automated curation of metabolic reconstructions. BMC Bioinform, 2007, 8: 212.

[33]

Schellenberger J, Que R, Fleming RM, Thiele I, Orth JD, Feist AM, Zielinski DC, Bordbar A, Lewis NE, Rahmanian S, . Quantitative prediction of cellular metabolism with constraint-based models: the COBRA Toolbox v2.0. Nat Protoc, 2011, 6: 1290-1307.

[34]

Schreiber F. High quality visualization of biochemical pathways in BioPath. In Silico Biol, 2002, 2: 59-73.

[35]

Schweizer E, Kottig H, Regler R, Rottner G. Genetic control of Yarrowia lipolytica fatty acid synthetase biosynthesis and function. J Basic Microbiol, 1988, 28: 283-292.

[36]

Scolnick EM, Lin EC. Parallel induction of d-arabitol and d-sorbitol dehydrogenases. J Bacteriol, 1962, 84: 631-637.

[37]

Sitepu I, Selby T, Lin T, Zhu S, Boundy-Mills K. Carbon source utilization and inhibitor tolerance of 45 oleaginous yeast species. J Ind Microbiol Biotechnol, 2014, 41: 1061-1070.

[38]

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

[39]

Toya Y, Shimizu H. Flux analysis and metabolomics for systematic metabolic engineering of microorganisms. Biotechnol Adv, 2013, 31: 818-826.

[40]

Wang Y, Xiao J, Suzek TO, Zhang J, Wang J, Bryant SH. PubChem: a public information system for analyzing bioactivities of small molecules. Nucleic Acids Res, 2009, 37: W623-W633.

[41]

Wang JJ, Zhang BR, Chen SL. Oleaginous yeast Yarrowia lipolytica mutants with a disrupted fatty acyl-CoA synthetase gene accumulate saturated fatty acid. Process Biochem, 2011, 46: 1436-1441.

[42]

Wang W, Wei H, Alahuhta M, Chen X, Hyman D, Johnson DK, Zhang M, Himmel ME. Heterologous expression of xylanase enzymes in lipogenic yeast Yarrowia lipolytica. PLoS ONE, 2014, 9: e111443.

[43]

Wehrspann P, Fullbrandt U. Report of a case of Yarrowia lipolytica (Wickerman et al.) van der Walt & von Arx isolated from a blood culture. Mykosen, 1985, 28: 217-222.

[44]

Ye C, Qiao W, Yu X, Ji X, Huang H, Collier JL, Liu L. Reconstruction and analysis of the genome-scale metabolic model of Schizochytrium limacinum SR21 for docosahexaenoic acid production. BMC Genomics, 2015, 16: 799.

[45]

Ye C, Xu N, Chen H, Chen YQ, Chen W, Liu L. Reconstruction and analysis of a genome-scale metabolic model of the oleaginous fungus Mortierella alpina. BMC Syst Biol, 2015, 9: 1.

[46]

Yen CLE, Monetti M, Burri BJ, Farese RV. The triacylglycerol synthesis enzyme DGAT1 also catalyzes the synthesis of diacylglycerols, waxes, and retinyl esters. J Lipid Res, 2005, 46: 1502-1511.

[47]

Yen CL, Stone SJ, Koliwad S, Harris C, Farese RV Jr. Thematic review series: glycerolipids. DGAT enzymes and triacylglycerol biosynthesis. J Lipid Res, 2008, 49: 2283-2301.

[48]

Yu LJ, Qin WM, Lan WZ, Zhou PP, Zhu M. Improved arachidonic acids production from the fungus Mortierella alpina by glutamate supplementation. Bioresour Technol, 2003, 88: 265-268.

[49]

Yu CS, Lin CJ, Hwang JK. Predicting subcellular localization of proteins for Gram-negative bacteria by support vector machines based on n-peptide compositions. Protein Sci, 2004, 13: 1402-1406.

[50]

Zhang C, Hua Q. Applications of genome-scale metabolic models in biotechnology and systems medicine. Front Physiol, 2015, 6: 413.

[51]

Zhang C, Ji B, Mardinoglu A, Nielsen J, Hua Q. Logical transformation of genome-scale metabolic models for gene level applications and analysis. Bioinformatics, 2015, 31: 2324-2331.

Funding

National Natural Science Foundation of China(21576089)

AI Summary AI Mindmap
PDF

119

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/