Metabolic engineering strategies for de novo biosynthesis of sterols and steroids in yeast

Yuehao Gu , Xue Jiao , Lidan Ye , Hongwei Yu

Bioresources and Bioprocessing ›› 2021, Vol. 8 ›› Issue (1) : 110

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Bioresources and Bioprocessing ›› 2021, Vol. 8 ›› Issue (1) : 110 DOI: 10.1186/s40643-021-00460-9
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Metabolic engineering strategies for de novo biosynthesis of sterols and steroids in yeast

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Abstract

Steroidal compounds are of great interest in the pharmaceutical field, with steroidal drugs as the second largest category of medicine in the world. Advances in synthetic biology and metabolic engineering have enabled de novo biosynthesis of sterols and steroids in yeast, which is a green and safe production route for these valuable steroidal compounds. In this review, we summarize the metabolic engineering strategies developed and employed for improving the de novo biosynthesis of sterols and steroids in yeast based on the regulation mechanisms, and introduce the recent progresses in de novo synthesis of some typical sterols and steroids in yeast. The remaining challenges and future perspectives are also discussed.

Keywords

Sterols and steroids / De novo biosynthesis / Yeast / Metabolic engineering

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Yuehao Gu, Xue Jiao, Lidan Ye, Hongwei Yu. Metabolic engineering strategies for de novo biosynthesis of sterols and steroids in yeast. Bioresources and Bioprocessing, 2021, 8(1): 110 DOI:10.1186/s40643-021-00460-9

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References

[1]

Abe F, Hiraki T. Mechanistic role of ergosterol in membrane rigidity and cycloheximide resistance in Saccharomyces cerevisiae. Biochim Biophys Acta Biomembr, 2009, 1788: 743-752.

[2]

Adeyo O, Horn PJ, Lee SK, Binns DD, Chandrahas A, Chapman KD, Goodman JM. The yeast lipin orthologue Pah1p is important for biogenesis of lipid droplets. J Cell Biol, 2011, 192: 1043-1055.

[3]

Alvarez-Vasquez F, Riezman H, Hannun YA, Voit EO. Mathematical modeling and validation of the ergosterol pathway in Saccharomyces cerevisiae. PLoS ONE, 2011, 6: e28344.

[4]

Arendt P, Miettinen K, Pollier J, De Rycke R, Callewaert N, Goossens A. An endoplasmic reticulum-engineered yeast platform for overproduction of triterpenoids. Metab Eng, 2017, 40: 165-175.

[5]

ArthingtonSkaggs BA, Crowell DN, Yang H, Sturley SL, Bard M. Positive and negative regulation of a sterol biosynthetic gene (ERG3) in the post-squalene portion of the yeast ergosterol pathway. FEBS Lett, 1996, 392: 161-165.

[6]

Auchus R, Miller W. de Montellano OP. P450 enzymes in steroid processing. Cytochrome P450, 2015, 4, Cham: Springer.

[7]

Baek M, DiMaio F, Anishchenko I, Dauparas J, Ovchinnikov S, Lee GR, Wang J, Cong Q, Kinch LN, Schaeffer RD, Millán C, Park H, Adams C, Glassman CR, DeGiovanni A, Pereira JH, Rodrigues AV, Dijk AAV, Ebrecht AC, Opperman DJ, Sagmeister T, Buhlheller C, Pavkov-Keller T, Rathinaswamy MK, Dalwadi U, Yip CK, Burke JE, Garcia KC, Grishin NV, Adams PD, Read RJ, Baker D. Accurate prediction of protein structures and interactions using a three-track neural network. Science, 2021, 373: 871-876.

[8]

Bikle DD. Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol, 2014, 21: 319-329.

[9]

Campbell K, Xia JY, Nielsen J. The impact of systems biology on bioprocessing. Trends Biotechnol, 2017, 35: 1156-1168.

[10]

Chen Y, Daviet L, Schalk M, Siewers V, Nielsen J. Establishing a platform cell factory through engineering of yeast acetyl-CoA metabolism. Metab Eng, 2013, 15: 48-54.

[11]

Cheng J, Chen J, Liu X, Li X, Zhang W, Dai Z, Lu L, Zhou X, Cai J, Zhang X, Jiang H, Ma Y. The origin and evolution of the diosgenin biosynthetic pathway in yam. Plant Commun, 2021, 2: 100079.

[12]

Choudhary V, Schneiter R. Lipid droplet biogenesis from specialized ER subdomains. Microb Cell, 2020, 7: 218-221.

[13]

Choudhary V, El Atab O, Mizzon G, Prinz WA, Schneiter R. Seipin and Nem1 establish discrete ER subdomains to initiate yeast lipid droplet biogenesis. J Cell Biol, 2020, 219: e201910177.

[14]

Christ B, Xu C, Xu M, Li FS, Wada N, Mitchell AJ, Han XL, Wen ML, Fujita M, Weng JK. Repeated evolution of cytochrome P450-mediated spiroketal steroid biosynthesis in plants. Nat Commun, 2019, 10: 3206.

[15]

Davies BSJ, Rine J. A role for sterol levels in oxygen sensing in Saccharomyces cerevisiae. Genetics, 2006, 174: 191-201.

[16]

Davies BSJ, Wang HS, Rine J. Dual activators of the sterol biosynthetic pathway of Saccharomyces cerevisiae: similar activation/regulatory domains but different response mechanisms. Mol Cell Biol, 2005, 25: 7375-7385.

[17]

Dey P, Kundu A, Chakraborty HJ, Kar B, Choi WS, Lee BM, Bhakta T, Atanasov AG, Kim HS. Therapeutic value of steroidal alkaloids in cancer: current trends and future perspectives. Int J Cancer, 2019, 145: 1731-1744.

[18]

Dong H, Chen S, Zhu JX, Gao K, Zha WL, Lin PC, Zi JC. Enhance production of diterpenoids in yeast by overexpression of the fused enzyme of ERG20 and its mutant mERG20. J Biotechnol, 2020, 307: 29-34.

[19]

Du HX, Xiao WH, Wang Y, Zhou X, Zhang Y, Liu D, Yuan YJ. Engineering Yarrowia lipolytica for campesterol overproduction. PLoS ONE, 2016, 11: e0146773.

[20]

Duport C, Spagnoli R, Degryse E, Pompon D. Self-sufficient biosynthesis of pregnenolone and progesterone in engineered yeast. Nat Biotechnol, 1998, 16: 186-189.

[21]

Duport C, Schoepp B, Chatelain E, Spagnoli R, Dumas B, Pompon D. Critical role of the plasma membrane for expression of mammalian mitochondrial side chain cleavage activity in yeast. Eur J Biochem, 2003, 270: 1502-1514.

[22]

Espenshade PJ, Hughes AL. Regulation of sterol synthesis in eukaryotes. Annu Rev Genet, 2007, 41: 401-427.

[23]

Fei WH, Shui GH, Gaeta B, Du XM, Kuerschner L, Li P, Brown AJ, Wenk MR, Parton RG, Yang HY. Fld1p, a functional homologue of human seipin, regulates the size of lipid droplets in yeast. J Cell Biol, 2008, 180: 473-482.

[24]

Fernandes P, Cruz A, Angelova B, Pinheiro HM, Cabral JMS. Microbial conversion of steroid compounds: recent developments. Enzyme Microb Tech, 2003, 32: 688-705.

[25]

Fernandez-Cabezon L, Galan B, Garcia JL. New insights on steroid biotechnology. Front Microbiol, 2018, 9: 958.

[26]

Gardner RG, Shan H, Matsuda SPT, Hampton RY. An oxysterol-derived positive signal for 3-hydroxy-3-methylglutaryl-CoA reductase degradation in yeast. J Biol Chem, 2001, 276: 8681-8694.

[27]

Guo XJ, Xiao WH, Wang Y, Yao MD, Zeng BX, Liu H, Zhao GR, Yuan YJ. Metabolic engineering of Saccharomyces cerevisiae for 7-dehydrocholesterol overproduction. Biotechnol Biofuels, 2018, 11: 192.

[28]

Hans-Peter H, Leber R, Martin L, Corinna O, Barbara P, Harald P, Birgit P (2021) Production of sterols in modified yeast. US patent 0,180,103, 17 Jun 2021

[29]

He XP, Zhang BR, Tan HR. Overexpression of a sterol C-24(28) reductase increases ergosterol production in Saccharomyces cerevisiae. Biotechnol Lett, 2003, 25: 773-778.

[30]

He XP, Guo XN, Liu N, Zhang BR. Ergosterol production from molasses by genetically modified Saccharomyces cerevisiae. Appl Microbiol Biot, 2007, 75: 55-60.

[31]

Heese-Peck A, Pichler H, Zanolari B, Watanabe R, Daum G, Riezman H. Multiple functions of sterols in yeast endocytosis. Mol Biol Cell, 2002, 13: 2664-2680.

[32]

Hirz M, Richter G, Leitner E, Wriessnegger T, Pichler H. A novel cholesterol-producing Pichia pastoris strain is an ideal host for functional expression of human Na, K-ATPase alpha 3 beta 1 isoform. Appl Microbiol Biot, 2013, 97: 9465-9478.

[33]

Hong J, Park SH, Kim S, Kim SW, Hahn JS. Efficient production of lycopene in Saccharomyces cerevisiae by enzyme engineering and increasing membrane flexibility and NAPDH production. Appl Microbiol Biot, 2019, 103: 211-223.

[34]

Hu ZH, He B, Ma L, Sun YL, Niu YL, Zeng B. Recent advances in ergosterol biosynthesis and regulation mechanisms in Saccharomyces cerevisiae. Indian J Microbiol, 2017, 57: 270-277.

[35]

Huang HP, Gao SL, Chen LL, Jiao XK. In vitro induction and identification of autotetraploids of Dioscorea zingiberensis. In Vitro Cell Dev-Pl, 2008, 44: 448-455.

[36]

Jacquier N, Schneiter R. Mechanisms of sterol uptake and transport in yeast. J Steroid Biochem, 2012, 129: 70-78.

[37]

Jandrositz A, Turnowsky F, Hogenauer G. The gene encoding squalene epoxidase from Saccharomyces Cerevisiae: cloning and characterization. Gene, 1991, 107: 155-160.

[38]

Jensen-Pergakes K, Guo ZM, Giattina M, Sturley SL, Bard M. Transcriptional regulation of the two sterol esterification genes in the yeast Saccharomyces cerevisiae. J Bacteriol, 2001, 183: 4950-4957.

[39]

Jiang LH, Huang L, Cai J, Xu ZN, Lian JZ. Functional expression of eukaryotic cytochrome P450s in yeast. Biotechnol Bioeng, 2021, 118: 1050-1065.

[40]

Johnston EJ, Moses T, Rosser SJ. The wide-ranging phenotypes of ergosterol biosynthesis mutants, and implications for microbial cell factories. Yeast, 2020, 37: 27-44.

[41]

Jorda T, Puig S. Regulation of ergosterol biosynthesis in Saccharomyces cerevisiae. Genes, 2020, 11: 795.

[42]

Jumper J, Evans R, Pritzel A, Green T, Figurnov M, Ronneberger O, Tunyasuvunakool K, Bates R, Zidek A, Potapenko A, Bridgland A, Meyer C, Kohl SAA, Ballard AJ, Cowie A, Romera-Paredes B, Nikolov S, Jain R, Adler J, Back T, Petersen S, Reiman D, Clancy E, Zielinski M, Steinegger M, Pacholska M, Berghammer T, Bodenstein S, Silver D, Vinyals O, Senior AW, Kavukcuoglu K, Kohli P, Hassabis D. Highly accurate protein structure prediction with AlphaFold. Nature, 2021, 596: 583-589.

[43]

Kim JE, Jang IS, Son SH, Ko YJ, Cho BK, Kim SC, Lee JY. Tailoring the Saccharomyces cerevisiae endoplasmic reticulum for functional assembly of terpene synthesis pathway. Metab Eng, 2019, 56: 50-59.

[44]

Kim GB, Kim WJ, Kim HU, Lee SY. Machine learning applications in systems metabolic engineering. Curr Opin Biotech, 2020, 64: 1-9.

[45]

King ZA, Feist AM. Optimal cofactor swapping can increase the theoretical yield for chemical production in Escherichia coli and Saccharomyces cerevisiae. Metab Eng, 2014, 24: 117-128.

[46]

Klinkenberg LG, Mennella TA, Luetkenhaus K, Zitomer RS. Combinatorial repression of the hypoxic genes of Saccharomyces cerevisiae by DNA binding proteins Rox1 and Mot3. Eukaryot Cell, 2005, 4: 649-660.

[47]

Koffel R, Tiwari R, Falquet L, Schneiter R. 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, 2005, 25: 1655-1668.

[48]

Kohlwein SD, Veenhuis M, van der Klei IJ. Lipid droplets and peroxisomes: key players in cellular lipid homeostasis or a matter of fat-store ‘em up or burn ‘em down. Genetics, 2013, 193: 1-50.

[49]

Kohut P, Wustner D, Hronska L, Kuchler K, Hapala I, Valachovic M. The role of ABC proteins Aus1p and Pdr11p in the uptake of external sterols in yeast: dehydroergosterol fluorescence study. Biochem Bioph Res Co, 2011, 404: 233-238.

[50]

Kovganko NV, Ananich SK. The chemical synthesis of sterols: latest advances. Chem Nat Compd, 1999, 35: 229-259.

[51]

Lang C, Veen M (2006) Preparation of 7-dehydrocholesterol and/or the biosynthetic intermediates and/or secondary products thereof in transgenic organisms. US Patent 0,240,508, 26 Oct 2006

[52]

Leber R, Landl K, Zinser E, Ahorn H, Spok A, Kohlwein SD, Turnowsky F, Daum G. Dual localization of squalene epoxidase, Erg1p, in yeast reflects a relationship between the endoplasmic reticulum and lipid particles. Mol Biol Cell, 1998, 9: 375-386.

[53]

Lian J, Si T, Nair NU, Zhao H. Design and construction of acetyl-CoA overproducing Saccharomyces cerevisiae strains. Metab Eng, 2014, 24: 139-149.

[54]

Liu GD, Chen Y, Faergeman NJ, Nielsen J. Elimination of the last reactions in ergosterol biosynthesis alters the resistance of Saccharomyces cerevisiae to multiple stresses. FEMS Yeast Res, 2017, 17: fox063.

[55]

Liu JF, Xia JJ, Nie KL, Wang F, Deng L. Outline of the biosynthesis and regulation of ergosterol in yeast. World J Microb Biot, 2019, 35: 98.

[56]

Liu GS, Li T, Zhou W, Jiang M, Tao XY, Liu M, Zhao M, Ren YH, Gao B, Wang FQ, Wei DZ. The yeast peroxisome: a dynamic storage depot and subcellular factory for squalene overproduction. Metab Eng, 2020, 57: 151-161.

[57]

Liu M, Lin YC, Guo JJ, Du MM, Tao XY, Gao B, Zhao M, Ma YS, Wang FQ, Wei DZ. High-level production of sesquiterpene patchoulol in Saccharomyces cerevisiae. Acs Synth Biol, 2021, 10: 158-172.

[58]

Luo YS, Nicaud JM, Van Veldhoven PP, Chardot T. The acyl-CoA oxidases from the yeast Yarrowia lipolytica: characterization of Aox2p. Arch Biochem Biophys, 2002, 407: 32-38.

[59]

Ma BX, Ke X, Tang XL, Zheng RC, Zheng YG. Rate-limiting steps in the Saccharomyces cerevisiae ergosterol pathway: towards improved ergosta-5,7-dien-3 beta-ol accumulation by metabolic engineering. World J Microb Biot, 2018, 34(4): 55.

[60]

Ma T, Shi B, Ye ZL, Li XW, Liu M, Chen Y, Xia J, Nielsen J, Deng ZX, Liu TG. Lipid engineering combined with systematic metabolic engineering of Saccharomyces cerevisiae for high-yield production of lycopene. Metab Eng, 2019, 52: 134-142.

[61]

Mlickova K, Roux E, Athenstaedt K, d'Andrea S, Daum G, Chardot T, Nicaud JM. Lipid accumulation, lipid body formation, and acyl coenzyme A oxidases of the yeast Yarrowia lipolytica. Appl Environ Microb, 2004, 70: 3918-3924.

[62]

Montanes FM, Pascual-Ahuir A, Proft M. Repression of ergosterol biosynthesis is essential for stress resistance and is mediated by the Hog1 MAP kinase and the Mot3 and Rox1 transcription factors. Mol Microbiol, 2011, 79: 1008-1023.

[63]

Nemoto H, Nagai M, Fukumoto K, Kametani T. A stereoselective total synthesis of 11-oxoprogesterone, a precursor to the corticosteroids, via an intramolecular cycloaddition reaction. J Chem Soc Perkin Trans, 1986, 1: 1621-1625.

[64]

Nohturfft A, Zhang SC. Coordination of lipid metabolism in membrane biogenesis. Annu Rev Cell Dev Bi, 2009, 25: 539-566.

[65]

Ohta T, Zhang HY, Torihara Y, Furukawa I. Improved synthetic route to dexamethasone acetate from tigogenin. Org Process Res Dev, 1997, 1: 420-424.

[66]

Palermo LM, Leak FW, Tove S, Parks LW. Assessment of the essentiality of ERG genes late in ergosterol biosynthesis in Saccharomyces cerevisiae. Curr Genet, 1997, 32: 93-99.

[67]

Paramasivan K, Mutturi S. Progress in terpene synthesis strategies through engineering of Saccharomyces cerevisiae. Crit Rev Biotechnol, 2017, 37: 974-989.

[68]

Paramasivan K, Mutturi S. Regeneration of NADPH coupled with HMG-CoA reductase activity increases squalene synthesis in Saccharomyces cerevisiae. J Agr Food Chem, 2017, 65: 8162-8170.

[69]

Park Y, Han GS, Mileykovskaya E, Garrett TA, Carman GM. Altered lipid synthesis by lack of yeast Pah1 phosphatidate phosphatase reduces chronological life span. J Biol Chem, 2015, 290: 25382-25394.

[70]

Ploier B, Korber M, Schmidt C, Koch B, Leitner E, Daum G. Regulatory link between steryl ester formation and hydrolysis in the yeast Saccharomyces cerevisiae. BBA Mol Cell Biol L, 2015, 1851: 977-986.

[71]

Polakowski T, Stahl U, Lang C. Overexpression of a cytosolic hydroxymethylglutaryl-CoA reductase leads to squalene accumulation in yeast. Appl Microbiol Biot, 1998, 49: 66-71.

[72]

Polakowski T, Bastl R, Stahl U, Lang C. Enhanced sterol-acyl transferase activity promotes sterol accumulation in Saccharomyces cerevisiae. Appl Microbiol Biot, 1999, 53: 30-35.

[73]

Qian YD, Tan SY, Dong GR, Niu YJ, Hu CY, Meng YH. Increased campesterol synthesis by improving lipid content in engineered Yarrowia lipolytica. Appl Microbiol Biot, 2020, 104: 7165-7175.

[74]

Quon E, Sere YY, Chauhan N, Johansen J, Sullivan DP, Dittman JS, Rice WJ, Chan RB, Di Paolo G, Beh CT, Menon AK. Endoplasmic reticulum-plasma membrane contact sites integrate sterol and phospholipid regulation. Plos Biol, 2018, 16: e2003864.

[75]

Rajakumari S, Grillitsch K, Daum G. Synthesis and turnover of non-polar lipids in yeast. Prog Lipid Res, 2008, 47: 157-171.

[76]

Saint-Prix F, Bonquist L, Dequin S. Functional analysis of the ALD gene family of Saccharomyces cerevisiae during anaerobic growth on glucose: the NADP(+)-dependent Ald6p and Ald5p isoforms play a major role in acetate formation. Microbiol Sgm, 2004, 150: 2209-2220.

[77]

Sambyal K, Singh RV. Production aspects of testosterone by microbial biotransformation and future prospects. Steroids, 2020, 159: 108651.

[78]

Sawai S, Ohyama K, Yasumoto S, Seki H, Sakuma T, Yamamoto T, Takebayashi Y, Kojima M, Sakakibara H, Aoki T, Muranaka T, Saito K, Umemoto N. Sterol side chain reductase 2 is a key enzyme in the biosynthesis of cholesterol, the common precursor of toxic steroidal glycoalkaloids in potato. Plant Cell, 2014, 26: 3763-3774.

[79]

Schmidt C, Athenstaedt K, Koch B, Ploier B, Korber M, Zellnig G, Daum G. Defects in triacylglycerol lipolysis affect synthesis of triacylglycerols and steryl esters in the yeast. BBA Mol Cell Biol L, 2014, 1841: 1393-1402.

[80]

Shakoury-Elizeh M, Protchenko O, Berger A, Cox J, Gable K, Dunn TM, Prinz WA, Bard M, Philpott CC. Metabolic response to iron deficiency in Saccharomyces cerevisiae. J Biol Chem, 2010, 285: 14823-14833.

[81]

Shin GH, Veen M, Stahl U, Lang C. Overexpression of genes of the fatty acid biosynthetic pathway leads to accumulation of sterols in Saccharomyces cerevisiae. Yeast, 2012, 29: 371-383.

[82]

Sorger D, Daum G. Triacylglycerol biosynthesis in yeast. Appl Microbiol Biot, 2003, 61: 289-299.

[83]

Souza CM, Schwabe TM, Pichler H, Ploier B, Leitner E, Guan XL, Wenk MR, Riezman I, Riezman H. A stable yeast strain efficiently producing cholesterol instead of ergosterol is functional for tryptophan uptake, but not weak organic acid resistance. Metab Eng, 2011, 13: 555-569.

[84]

Su W, Xiao WH, Wang Y, Liu D, Zhou X, Yuan YJ. Alleviating redox imbalance enhances 7-dehydrocholesterol production in engineered Saccharomyces cerevisiae. PLoS ONE, 2015, 10: e0130840.

[85]

Szczebara FM, Chandelier C, Villeret C, Masurel A, Bourot S, Duport C, Blanchard S, Groisillier A, Testet E, Costaglioli P, Cauet G, Degryse E, Balbuena D, Winter J, Achstetter T, Spagnoli R, Pompon D, Dumas B. Total biosynthesis of hydrocortisone from a simple carbon source in yeast. Nat Biotechnol, 2003, 21: 143-149.

[86]

Takahashi H, McCaffery JM, Irizarry RA, Boeke JD. Nucleocytosolic acetyl-coenzyme a synthetase is required for histone acetylation and global transcription. Mol Cell, 2006, 23: 207-217.

[87]

Tan TW, Zhang M, Gao H. Ergosterol production by fed-batch fermentation of Saccharomyces cerevisiae. Enzyme Microb Tech, 2003, 33: 366-370.

[88]

Tang XL, Feng HX, Chen WN. Metabolic engineering for enhanced fatty acids synthesis in Saccharomyces cerevisiae. Metab Eng, 2013, 16: 95-102.

[89]

Tantuco K, Deretey E, Csizmadia IG. Stabilities for the eight isomeric forms of the steroid skeleton (perhydrocyclopentanophenanthrene). J Mol Struc-Theochem, 2000, 503: 97-111.

[90]

Tiwari R, Koffel R, Schneiter R. An acetylation/deacetylation cycle controls the export of sterols and steroids from S. cerevisiae. EMBO J, 2007, 26: 5109-5119.

[91]

Tsukagoshi Y, Suzuki H, Seki H, Muranaka T, Ohyama K, Fujimoto Y. Ajuga 24-sterol reductase catalyzes the direct reductive conversion of 24-methylenecholesterol to campesterol. J Biol Chem, 2016, 291: 8189-8198.

[92]

Veen M, Stahl U, Lang C. Combined overexpression of genes of the ergosterol biosynthetic pathway leads to accumulation of sterols in Saccharomyces cerevisiae. FEMS Yeast Res, 2003, 4: 87-95.

[93]

Vemuri GN, Eiteman MA, McEwen JE, Olsson L, Nielsen J. Increasing NADH oxidation reduces overflow metabolism in Saccharomyces cerevisiae. P Natl Acad Sci USA, 2007, 104: 2402-2407.

[94]

Vik A, Rine J. Upc2p and Ecm22p, dual regulators of sterol biosynthesis in Saccharomyces cerevisiae. Mol Cell Biol, 2001, 21: 6395-6405.

[95]

Wagner A, Grillitsch K, Leitner E, Daum G. Mobilization of steryl esters from lipid particles of the yeast Saccharomyces cerevisiae. BBA Mol Cell Biol L, 2009, 1791: 118-124.

[96]

Wang FQ, Li B, Wang W, Zhang CG, Wei DZ. Biotransformation of diosgenin to nuatigenin-type steroid by a newly isolated strain, Streptomyces virginiae IBL-14. Appl Microbiol Biot, 2007, 77: 771-777.

[97]

Wang SQ, Wang T, Liu JF, Deng L, Wang F. Overexpression of Ecm22 improves ergosterol biosynthesis in Saccharomyces cerevisiae. Lett Appl Microbiol, 2018, 67: 484-490.

[98]

Wei LJ, Kwak S, Liu JJ, Lane S, Hua Q, Kweon DH, Jin YS. Improved squalene production through increasing lipid contents in Saccharomyces cerevisiae. Biotechnol Bioeng, 2018, 115: 1793-1800.

[99]

Wriessnegger T, Pichler H. Yeast metabolic engineering-targeting sterol metabolism and terpenoid formation. Prog Lipid Res, 2013, 52: 277-293.

[100]

Xu SH, Li YR. Yeast as a promising heterologous host for steroid bioproduction. J J Ind Microbiol Biot, 2020, 47: 829-843.

[101]

Xu SH, Chen C, Li YR. Engineering of phytosterol-producing yeast platforms for functional reconstitution of downstream biosynthetic pathways. Acs Synth Biol, 2020, 9: 3157-3170.

[102]

Yang HY, Bard M, Bruner DA, Gleeson A, Deckelbaum RJ, Aljinovic G, Pohl TM, Rothstein R, Sturley SL. Sterol esterification in yeast: a two-gene process. Science, 1996, 272: 1353-1356.

[103]

Yin Y, Gao LH, Zhang XN, Gao W. A cytochrome P450 monooxygenase responsible for the C-22 hydroxylation step in the Paris polyphylla steroidal saponin biosynthesis pathway. Phytochemistry, 2018, 156: 116-123.

[104]

Zhang S, Sakuradani E, Shimizu S. Identification of a sterol Δ7 reductase gene involved in desmosterol biosynthesis in Mortierella alpina 1S–4. Appl Environ Microb, 2007, 73: 1736-1741.

[105]

Zhang Y, Wang Y, Yao MD, Liu H, Zhou X, Xiao WH, Yuan YJ. Improved campesterol production in engineered Yarrowia lipolytica strains. Biotechnol Lett, 2017, 39: 1033-1039.

[106]

Zhang RS, Zhang Y, Wang Y, Yao MD, Zhang JL, Liu H, Zhou X, Xiao WH, Yuan YJ. Pregnenolone overproduction in Yarrowia lipolytica by integrative components pairing of the cytochrome P450scc system. Acs Synth Biol, 2019, 8: 2666-2678.

[107]

Zhao X, Shi F, Zhan W. Overexpression of ZWF1 and POS5 improves carotenoid biosynthesis in recombinant Saccharomyces cerevisiae. Lett Appl Microbiol, 2015, 61: 354-360.

[108]

Zhu ZW, Ding YF, Gong ZW, Yang L, Zhang SF, Zhang CY, Lin XP, Shen HW, Zou HF, Xie ZS, Yang FQ, Zhao XD, Liu PS, Zhao ZBK. Dynamics of the lipid droplet proteome of the oleaginous yeast Rhodosporidium toruloides. Eukaryot Cell, 2015, 14: 252-264.

[109]

Zinser E, Paltauf F, Daum G. Sterol composition of yeast organelle membranes and subcellular-distribution of enzymes involved in sterol-metabolism. J Bacteriol, 1993, 175: 2853-2858.

Funding

National Key Research and Development Program of China(2018YFA0901800)

Natural Science Foundation of Zhejiang Province(LZ20B060002)

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