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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志  2022, Vol. 42 Issue (1/2): 1-13    DOI: 10.13523/j.cb.2111009
工业微生物的设计、改造与应用专题     
抑制剂耐受性酵母底盘细胞的设计与构建*
陈涛1,2,刘志华1,2,李霞1,2,谢泽雄1,2,**()
1 教育部合成生物学前沿科学中心和系统生物工程重点实验室 天津 300072
2 天津大学化工学院 天津 300072
Design and Construction of Inhibitor-tolerant Yeast Chassis Cells
CHEN Tao1,2,LIU Zhi-hua1,2,LI Xia1,2,XIE Ze-xiong1,2,**()
1 Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering, Ministry of Education, Tianjin 300072, China
2 Collaborative Innovation Center of Chemical Science and Engineering, Tianjin University, Tianjin 300072, China
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摘要:

纤维素乙醇是一种低碳清洁的绿色能源,可与传统石油基液体燃料混合使用,具备广阔的应用前景。纤维素乙醇的生产历经木质纤维素预处理、糖化和酿酒酵母发酵等工艺,而预处理过程会产生多种副产物,显著抑制酵母细胞的生长速率和发酵性能。因此,构建抑制剂耐受性酵母底盘细胞,有助于提高纤维素乙醇的生产效率,降低生产成本。针对抑制剂耐受性酵母底盘细胞的设计与构建开展综述,系统总结了抑制剂的作用机制、耐受性底盘细胞的强化手段、抑制剂耐受性基因挖掘方法,并探讨了人工基因组重排提升酵母耐受性的最新进展。

关键词: 纤维素乙醇酿酒酵母抑制剂人工基因组重排    
Abstract:

Cellulosic ethanol, a low-carbon, clean and green energy, has broad application prospects. It can be mixed with traditional petroleum-based liquid fuels. The production of cellulosic ethanol goes through processes such as lignocellulose pretreatment, saccharification and Saccharomyces cerevisiae fermentation. However, the pretreatment process will produce many by-products, which significantly inhibit the growth rate and fermentation performance of yeast. Therefore, constructing inhibitor-tolerant yeast chassis cells can contribute to improving the production efficiency of cellulosic ethanol and reduce production costs. A review is conducted on the design and construction of inhibitor-tolerant yeast chassis cells, the mechanism of inhibitors, the methods of strengthening tolerant chassis cells, and means for mining inhibitor-tolerant genes. Finally, the latest progress in SCRaMbLE to improve yeast tolerance is discussed.

Key words: Cellulosic ethanol    Saccharomyces cerevisiae    Inhibitor    SCRaMbLE
收稿日期: 2021-11-02 出版日期: 2022-03-03
ZTFLH:  Q819  
基金资助: * 国家自然科学基金(2190070287);天津市科技计划资助项目(20JCQNJC02090)
通讯作者: 谢泽雄     E-mail: xzx@tju.edu.cn
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引用本文:

陈涛,刘志华,李霞,谢泽雄. 抑制剂耐受性酵母底盘细胞的设计与构建*[J]. 中国生物工程杂志, 2022, 42(1/2): 1-13.

CHEN Tao,LIU Zhi-hua,LI Xia,XIE Ze-xiong. Design and Construction of Inhibitor-tolerant Yeast Chassis Cells. China Biotechnology, 2022, 42(1/2): 1-13.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2111009        https://manu60.magtech.com.cn/biotech/CN/Y2022/V42/I1/2/1

预处理方法 条件 抑制剂浓度
酸预处理 0.5%硫酸,184℃,10 min,1 MPa 0.7 g/kg糠醛、2.1 g/kg羟甲基糠醛、12.6 g/kg乙酸[5]
碱预处理 6.5 g/L碳酸钠,195℃,10 min,1.2 MPa 0.4~1.2 g/kg酚类单体[6]
水热预处理 200℃,24 min 13.1 g/L乙酸,4.1 g/L糠醛、羟甲基糠醛,1.3g/L酚类物质[9]
汽爆预处理 1%硫酸,190℃, 5 min 5 g/L乙酸、4 g/L甲酸、1 g/L糠醛、1 g/L羟甲基糠醛[7]
氨爆破预处理 1∶1氨气/生物质,60%水负荷,130℃,15 min 4.61 g/L乙酸、0.912 g/L甲酸、0.003 g/L糠醛[10]
表1  不同预处理方法产生的抑制剂
图1  抑制剂对酵母的抑制作用及应对机制
抑制作用 抑制剂
细胞酸化及ATP损失 弱酸[21]
氧化还原失衡 呋喃[22]、酚类[23,24]
活性氧积累 呋喃[25]、弱酸[26]、酚类[24]
细胞膜和细胞壁完整性 弱酸[27]、酚类[28]
表2  酵母所受抑制作用及相应的抑制剂
图2  适应性进化示意图
图3  数量性状基因座分析示意图
图4  人工基因组重排示意图
[1] 李克强. 政府工作报告——2021年3月5日在第十三届全国人民代表大会第四次会议上.[2021-03-05]. http://www.xinhuanet.com/politics/2021lh/2021-03/12/c_1127205339.htm.
Li K Q. Government Work Report:at the fourth session of the 13th National People’s Congress on March 5, 2021.[2021-03-05]. http://www.xinhuanet.com/politics/2021lh/2021-03/12/c_1127205339.htm.
[2] Cunha J T, Soares P O, Baptista S L, et al. Engineered Saccharomyces cerevisiae for lignocellulosic valorization: a review and perspectives on bioethanol production. Bioengineered, 2020, 11(1):883-903.
doi: 10.1080/21655979.2020.1801178
[3] Alvira P, Tomás-Pejó E, Ballesteros M, et al. Pretreatment technologies for an efficient bioethanol production process based on enzymatic hydrolysis: a review. Bioresource Technology, 2010, 101(13):4851-4861.
doi: 10.1016/j.biortech.2009.11.093 pmid: 20042329
[4] Hu F, Ragauskas A. Pretreatment and lignocellulosic chemistry. BioEnergy Research, 2012, 5(4):1043-1066.
doi: 10.1007/s12155-012-9208-0
[5] Karimi K, Kheradmandinia S, Taherzadeh M J. Conversion of rice straw to sugars by dilute-acid hydrolysis. Biomass and Bioenergy, 2006, 30(3):247-253.
doi: 10.1016/j.biombioe.2005.11.015
[6] Klinke H B, Ahring B K, Schmidt A S, et al. Characterization of degradation products from alkaline wet oxidation of wheat straw. Bioresource Technology, 2002, 82(1):15-26.
doi: 10.1016/S0960-8524(01)00152-3
[7] Cara C, Ruiz E, Ballesteros M, et al. Production of fuel ethanol from steam-explosion pretreated olive tree pruning. Fuel, 2008, 87(6):692-700.
doi: 10.1016/j.fuel.2007.05.008
[8] Brandt B A, Jansen T, Görgens J F, et al. Overcoming lignocellulose-derived microbial inhibitors: advancing the Saccharomyces cerevisiae resistance toolbox. Biofuels, Bioproducts and Biorefining, 2019, 13(6):1520-1536.
doi: 10.1002/bbb.v13.6
[9] Kim Y, Ximenes E, Mosier N S, et al. Soluble inhibitors/deactivators of cellulase enzymes from lignocellulosic biomass. Enzyme and Microbial Technology, 2011, 48(4-5):408-415.
doi: 10.1016/j.enzmictec.2011.01.007
[10] Chundawat S P S, Vismeh R, Sharma L N, et al. Multifaceted characterization of cell wall decomposition products formed during ammonia fiber expansion (AFEX) and dilute acid based pretreatments. Bioresource Technology, 2010, 101(21):8429-8438.
doi: 10.1016/j.biortech.2010.06.027 pmid: 20598525
[11] 杨莉, 谭丽萍, 刘同军. 木质纤维素预处理抑制物产生及脱除方法的研究进展. 生物工程学报, 2021, 37(1):15-29.
Yang L, Tan L P, Liu T J. Progress in detoxification of inhibitors generated during lignocellulose pretreatment. Chinese Journal of Biotechnology, 2021, 37(1):15-29.
[12] Persson P, Andersson J, Gorton L, et al. Effect of different forms of alkali treatment on specific fermentation inhibitors and on the fermentability of lignocellulose hydrolysates for production of fuel ethanol. Journal of Agricultural and Food Chemistry, 2002, 50(19):5318-5325.
pmid: 12207468
[13] Nilvebrant N O, Persson P, Reimann A, et al. Limits for alkaline detoxification of dilute-acid lignocellulose hydrolysates. Applied Biochemistry and Biotechnology, 2003, 107(1-3):615-628.
doi: 10.1385/ABAB:107:1-3
[14] Xie R, Tu M B, Carvin J, et al. Detoxification of biomass hydrolysates with nucleophilic amino acids enhances alcoholic fermentation. Bioresource Technology, 2015, 186:106-113.
doi: 10.1016/j.biortech.2015.03.030
[15] Brás T, Guerra V, Torrado I, et al. Detoxification of hemicellulosic hydrolysates from extracted olive pomace by diananofiltration. Process Biochemistry, 2014, 49(1):173-180.
doi: 10.1016/j.procbio.2013.09.017
[16] Tomek K J, Saldarriaga C R C, Velasquez F P C, et al. Removal and upgrading of lignocellulosic fermentation inhibitors by in situ biocatalysis and liquid-liquid extraction. Biotechnology and Bioengineering, 2015, 112(3):627-632.
doi: 10.1002/bit.25473 pmid: 25311910
[17] He L W, Wang C, Shi H H, et al. Combination of steam explosion pretreatment and anaerobic alkalization treatment to improve enzymatic hydrolysis of Hippophae rhamnoides. Bioresource Technology, 2019, 289:121693.
doi: 10.1016/j.biortech.2019.121693
[18] Aghazadeh M, Ladisch M R, Engelberth A S. Acetic acid removal from corn stover hydrolysate using ethyl acetate and the impact on Saccharomyces cerevisiae bioethanol fermentation. Biotechnology Progress, 2016, 32(4):929-937.
doi: 10.1002/btpr.2282 pmid: 27090191
[19] Jin M J, Lau M W, Balan V, et al. Two-step SSCF to convert AFEX-treated switchgrass to ethanol using commercial enzymes and Saccharomyces cerevisiae 424A(LNH-ST). Bioresource Technology, 2010, 101(21):8171-8178.
doi: 10.1016/j.biortech.2010.06.026
[20] Nichols N N, Sharma L N, Mowery R A, et al. Fungal metabolism of fermentation inhibitors present in corn stover dilute acid hydrolysate. Enzyme and Microbial Technology, 2008, 42(7):624-630.
doi: 10.1016/j.enzmictec.2008.02.008
[21] Ullah A, Orij R, Brul S, et al. Quantitative analysis of the modes of growth inhibition by weak organic acids in Saccharomyces cerevisiae. Applied and Environmental Microbiology, 2012, 78(23):8377-8387.
doi: 10.1128/AEM.02126-12
[22] Ask M, Bettiga M, Mapelli V, et al. The influence of HMF and furfural on redox-balance and energy-state of xylose-utilizing Saccharomyces cerevisiae. Biotechnology for Biofuels, 2013, 6(1):1-13.
doi: 10.1186/1754-6834-6-1
[23] Adeboye P T, Bettiga M, Olsson L. ALD5, PAD1, ATF1 and ATF2 facilitate the catabolism of coniferyl aldehyde, ferulic acid and p-coumaric acid in Saccharomyces cerevisiae. Scientific Reports, 2017, 7:42635.
doi: 10.1038/srep42635
[24] Nguyen T T M, Iwaki A, Ohya Y, et al. Vanillin causes the activation of Yap1 and mitochondrial fragmentation in Saccharomyces cerevisiae. Journal of Bioscience and Bioengineering, 2014, 117(1):33-38.
doi: 10.1016/j.jbiosc.2013.06.008 pmid: 23850265
[25] Kim D, Hahn J S. Roles of the Yap1 transcription factor and antioxidants in Saccharomyces cerevisiae’s tolerance to furfural and 5-hydroxymethylfurfural, which function as thiol-reactive electrophiles generating oxidative stress. Applied and Environmental Microbiology, 2013, 79(16):5069-5077.
doi: 10.1128/AEM.00643-13
[26] Guo Z P, Olsson L. Physiological response of Saccharomyces cerevisiae to weak acids present in lignocellulosic hydrolysate. FEMS Yeast Research, 2014, 14(8):1234-1248.
doi: 10.1111/fyr.2014.14.issue-8
[27] Godinho C P, Prata C S, Pinto S N, et al. Pdr18 is involved in yeast response to acetic acid stress counteracting the decrease of plasma membrane ergosterol content and order. Scientific Reports, 2018, 8:7860.
doi: 10.1038/s41598-018-26128-7
[28] Campos F M, Couto J A, Figueiredo A R, et al. Cell membrane damage induced by phenolic acids on wine lactic acid bacteria. International Journal of Food Microbiology, 2009, 135(2):144-151.
doi: 10.1016/j.ijfoodmicro.2009.07.031 pmid: 19733929
[29] Garay-Arroyo A, Covarrubias A A, Clark I, et al. Response to different environmental stress conditions of industrial and laboratory Saccharomyces cerevisiae strains. Applied Microbiology and Biotechnology, 2004, 63(6):734-741.
pmid: 12910327
[30] Graves T, Narendranath N V, Dawson K, et al. Effect of pH and lactic or acetic acid on ethanol productivity by Saccharomyces cerevisiae in corn mash. Journal of Industrial Microbiology and Biotechnology, 2006, 33(6):469-474.
pmid: 16491359
[31] Stratford M, Nebe-Von-caron G, Steels H, et al. Weak-acid preservatives: pH and proton movements in the yeast Saccharomyces cerevisiae. International Journal of Food Microbiology, 2013, 161(3):164-171.
doi: 10.1016/j.ijfoodmicro.2012.12.013 pmid: 23334094
[32] Pampulha M E, Loureiro-Dias M C. Activity of glycolytic enzymes of Saccharomyces cerevisiae in the presence of acetic acid. Applied Microbiology and Biotechnology, 1990, 34(3):375-380.
[33] Allen S A, Clark W, McCaffery J M, et al. Furfural induces reactive oxygen species accumulation and cellular damage in Saccharomyces cerevisiae. Biotechnology for Biofuels, 2010, 3:2.
doi: 10.1186/1754-6834-3-2
[34] Castillo Agudo L. Lipid content of Saccharomyces cerevisiae strains with different degrees of ethanol tolerance. Applied Microbiology and Biotechnology, 1992, 37(5):647-651.
doi: 10.1007/BF00240742
[35] Aguilera F, Peinado R A, Millán C, et al. Relationship between ethanol tolerance, H+-ATPase activity and the lipid composition of the plasma membrane in different wine yeast strains. International Journal of Food Microbiology, 2006, 110(1):34-42.
pmid: 16690148
[36] Simões T, Mira N P, Fernandes A R, et al. The SPI1 gene, encoding a glycosylphosphatidylinositol-anchored cell wall protein, plays a prominent role in the development of yeast resistance to lipophilic weak-acid food preservatives. Applied and Environmental Microbiology, 2006, 72(11):7168-7175.
pmid: 16980434
[37] Ding M Z, Wang X, Yang Y, et al. Metabolomic study of interactive effects of phenol, furfural, and acetic acid on Saccharomyces cerevisiae. Omics, 2011, 15(10):647-653.
doi: 10.1089/omi.2011.0003
[38] Sauer U. Evolutionary engineering of industrially important microbial phenotypes. Advances in Biochemical Engineering/Biotechnology, 2001, 73:129-169. DOI: 10.1007/3-540-45300-8_7.
doi: 10.1007/3-540-45300-8_7
[39] Wang X, Li B Z, Ding M Z, et al. Metabolomic analysis reveals key metabolites related to the rapid adaptation of Saccharomyce cerevisiae to multiple inhibitors of furfural, acetic acid, and phenol. OMICS: A Journal of Integrative Biology, 2013, 17(3):150-159.
doi: 10.1089/omi.2012.0093
[40] Li W C, Zhu J Q, Zhao X, et al. Improving co-fermentation of glucose and xylose by adaptive evolution of engineering xylose-fermenting Saccharomyces cerevisiae and different fermentation strategies. Renewable Energy, 2019, 139:1176-1183.
doi: 10.1016/j.renene.2019.03.028
[41] Narayanan V, Sànchez I Nogué V, van Niel E W J, et al. Adaptation to low pH and lignocellulosic inhibitors resulting in ethanolic fermentation and growth of Saccharomyces cerevisiae. AMB Express, 2016, 6(1):59.
doi: 10.1186/s13568-016-0234-8
[42] Pereira F B, Romaní A, Ruiz H A, et al. Industrial robust yeast isolates with great potential for fermentation of lignocellulosic biomass. Bioresource Technology, 2014, 161:192-199.
doi: 10.1016/j.biortech.2014.03.043
[43] Della-Bianca B E, Gombert A K. Stress tolerance and growth physiology of yeast strains from the Brazilian fuel ethanol industry. Antonie Van Leeuwenhoek, 2013, 104(6):1083-1095.
doi: 10.1007/s10482-013-0030-2 pmid: 24062068
[44] de Witt R N, Kroukamp H, Volschenk H. Proteome response of two natural strains of Saccharomyces cerevisiae with divergent lignocellulosic inhibitor stress tolerance. FEMS Yeast Research, 2019, 19(1):foy116.
[45] Li Y X, Wu Y, Ma L, et al. Loss of heterozygosity by SCRaMbLEing. Science China Life Sciences, 2019, 62(3):381-393.
doi: 10.1007/s11427-019-9504-5
[46] Winkler J D, Kao K C. Recent advances in the evolutionary engineering of industrial biocatalysts. Genomics, 2014, 104(6):406-411.
doi: 10.1016/j.ygeno.2014.09.006
[47] Mans R, Daran J M G, Pronk J T. Under pressure: evolutionary engineering of yeast strains for improved performance in fuels and chemicals production. Current Opinion in Biotechnology, 2018, 50:47-56.
doi: 10.1016/j.copbio.2017.10.011
[48] Earl A M, Mohundro M M, Mian I S, et al. The IrrE protein of Deinococcus radiodurans R1 is a novel regulator of recA expression. Journal of Bacteriology, 2002, 184(22):6216-6224.
doi: 10.1128/JB.184.22.6216-6224.2002
[49] Lu H M, Gao G J, Xu G Z, et al. Deinococcus radiodurans PprI switches on DNA damage response and cellular survival networks after radiation damage. Molecular & Cellular Proteomics, 2009, 8(3):481-494.
doi: 10.1074/mcp.M800123-MCP200
[50] Wang L, Wang X, He Z Q, et al. Engineering prokaryotic regulator IrrE to enhance stress tolerance in budding yeast. Biotechnology for Biofuels, 2020, 13(1):193.
doi: 10.1186/s13068-020-01833-6
[51] Gutmann F, Jann C, Pereira F, et al. CRISPRi screens reveal genes modulating yeast growth in lignocellulose hydrolysate. Biotechnology for Biofuels, 2021, 14(1):41.
doi: 10.1186/s13068-021-01880-7
[52] Chen H Q, Li J, Wan C, et al. Improvement of inhibitor tolerance in Saccharomyces cerevisiae by overexpression of the quinone oxidoreductase family gene YCR102C. FEMS Yeast Research, 2019, 19(6):foz055.
doi: 10.1093/femsyr/foz055
[53] Swinnen S, Thevelein J M, Nevoigt E. Genetic mapping of quantitative phenotypic traits in Saccharomyces cerevisiae. FEMS Yeast Research, 2012, 12(2):215-227.
doi: 10.1111/j.1567-1364.2011.00777.x pmid: 22150948
[54] Zhang Y X, Perry K, Vinci V A, et al. Genome shuffling leads to rapid phenotypic improvement in bacteria. Nature, 2002, 415(6872):644-646.
doi: 10.1038/415644a
[55] Crameri A, Raillard S A, Bermudez E, et al. DNA shuffling of a family of genes from diverse species accelerates directed evolution. Nature, 1998, 391(6664):288-291.
doi: 10.1038/34663
[56] Chen L, Xin Q H, Ma L M, et al. Applications and research advance of genome shuffling for industrial microbial strains improvement. World Journal of Microbiology and Biotechnology, 2020, 36(10):1-8.
doi: 10.1007/s11274-019-2775-x
[57] Wang W T, Wu B, Qin H, et al. Genome shuffling enhances stress tolerance of Zymomonas mobilis to two inhibitors. Biotechnology for Biofuels, 2019, 12:288.
doi: 10.1186/s13068-019-1631-4
[58] Ren X L, Wang J C, Yu H, et al. Anaerobic and sequential aerobic production of high-titer ethanol and single cell protein from NaOH-pretreated corn stover by a genome shuffling-modified Saccharomyces cerevisiae strain. Bioresource Technology, 2016, 218:623-630.
doi: 10.1016/j.biortech.2016.06.118
[59] Wei P Y, Li Z L, He P, et al. Genome shuffling in the ethanologenic yeast Candida krusei to improve acetic acid tolerance. Biotechnology and Applied Biochemistry, 2008, 49(Pt 2):113-120.
doi: 10.1042/BA20070072
[60] Magocha T A, Zabed H, Yang M M, et al. Improvement of industrially important microbial strains by genome shuffling: Current status and future prospects. Bioresource Technology, 2018, 257:281-289.
doi: 10.1016/j.biortech.2018.02.118
[61] Wang Y M, Zhang G Y, Zhao X, et al. Genome shuffling improved the nucleosides production in Cordyceps kyushuensis. Journal of Biotechnology, 2017, 260:42-47.
doi: 10.1016/j.jbiotec.2017.08.021
[62] Zhang M M, Xiong L, Tang Y J, et al. Enhanced acetic acid stress tolerance and ethanol production in Saccharomyces cerevisiae by modulating expression of the de novo purine biosynthesis genes. Biotechnology for Biofuels, 2019, 12:116.
doi: 10.1186/s13068-019-1456-1
[63] Abdalla M, Eltayb W A, Yousif A. Comparison of structures among Saccharomyces cerevisiae Grxs proteins. Genes and Environment, 2018, 40:17.
doi: 10.1186/s41021-018-0104-5 pmid: 30186535
[64] Chen Y Y, Sheng J Y, Jiang T, et al. Transcriptional profiling reveals molecular basis and novel genetic targets for improved resistance to multiple fermentation inhibitors in Saccharomyces cerevisiae. Biotechnology for Biofuels, 2016, 9:9.
doi: 10.1186/s13068-015-0418-5
[65] Liu H M, Liu K, Yan M, et al. gTME for improved adaptation of Saccharomyces cerevisiae to corn cob acid hydrolysate. Applied Biochemistry and Biotechnology, 2011, 164(7):1150-1159.
doi: 10.1007/s12010-011-9201-7
[66] Parts L, Cubillos F A, Warringer J, et al. Revealing the genetic structure of a trait by sequencing a population under selection. Genome Research, 2011, 21(7):1131-1138.
doi: 10.1101/gr.116731.110
[67] Hu X H, Wang M H, Tan T, et al. Genetic dissection of ethanol tolerance in the budding yeast Saccharomyces cerevisiae. Genetics, 2007, 175(3):1479-1487.
pmid: 17194785
[68] Deparis Q, Claes A, Foulquié-Moreno M R, et al. Engineering tolerance to industrially relevant stress factors in yeast cell factories. FEMS Yeast Research, 2017, 17(4):fox036.
[69] Fernández-Niño M, Pulido S, Stefanoska D, et al. Identification of novel genes involved in acetic acid tolerance of Saccharomyces cerevisiae using pooled-segregant RNA sequencing. FEMS Yeast Research, 2018, 18(8):foy100.
[70] Meijnen J P, Randazzo P, Foulquié-Moreno M R, et al. Polygenic analysis and targeted improvement of the complex trait of high acetic acid tolerance in the yeast Saccharomyces cerevisiae. Biotechnology for Biofuels, 2016, 9:5.
doi: 10.1186/s13068-015-0421-x
[71] González-Ramos D, Gorter de Vries A R, Grijseels S S, et al. A new laboratory evolution approach to select for constitutive acetic acid tolerance in Saccharomyces cerevisiae and identification of causal mutations. Biotechnology for Biofuels, 2016, 9:173.
doi: 10.1186/s13068-016-0583-1 pmid: 27525042
[72] Maurer M J, Sutardja L, Pinel D, et al. Quantitative trait loci (QTL)-guided metabolic engineering of a complex trait. ACS Synthetic Biology, 2017, 6(3):566-581.
doi: 10.1021/acssynbio.6b00264
[73] Dymond J S, Richardson S M, Coombes C E, et al. Synthetic chromosome arms function in yeast and generate phenotypic diversity by design. Nature, 2011, 477(7365):471-476.
doi: 10.1038/nature10403
[74] Shen Y, Wang Y, Chen T, et al. Deep functional analysis of synII, a 770-kilobase synthetic yeast chromosome. Science, 2017, 355(6329). DOI: 10.1126/science.aaf4791.
doi: 10.1126/science.aaf4791
[75] Annaluru N, Muller H, Mitchell L A, et al. Total synthesis of a functional designer eukaryotic chromosome. Science, 2014, 344(6179):55-58.
doi: 10.1126/science.1249252
[76] Xie Z X, Li B Z, Mitchell L A, et al. “Perfect” designer chromosome V and behavior of a ring derivative. Science, 2017, 355(6329):eaaf4704.
doi: 10.1126/science.aaf4704
[77] Mitchell L A, Wang A, Stracquadanio G, et al. Synthesis, debugging, and effects of synthetic chromosome consolidation: synVI and beyond. Science, 2017, 355(6329). DOI: 10.1126/science.aaf4831.
doi: 10.1126/science.aaf4831
[78] Wu Y, Li B Z, Zhao M, et al. Bug mapping and fitness testing of chemically synthesized chromosome X. Science, 2017, 355(6329):1-6.
[79] Zhang W M, Zhao G H, Luo Z Q, et al. Engineering the ribosomal DNA in a megabase synthetic chromosome. Science, 2017, 355(6329):1-7.
[80] Hoess R H, Wierzbicki A, Abremski K. The role of the loxP spacer region in PI site-specific recombination. Nucleic Acids Research, 1986, 14(5):2287-2300.
pmid: 3457367
[81] Dymond J, Boeke J. The Saccharomyces cerevisiae SCRaMbLE system and genome minimization. Bioengineered, 2012, 3(3):170-173.
doi: 10.4161/bbug.19543
[82] Wang J, Xie Z X, Ma Y, et al. Ring synthetic chromosome V SCRaMbLE. Nature Communications, 2018, 9(1):3783.
doi: 10.1038/s41467-018-06216-y
[83] 谢泽雄, 陈祥荣, 肖文海, 等. 基因组再造与重排构建细胞工厂. 化工学报, 2019, 70(10):3712-3721.
Xie Z X, Chen X R, Xiao W H, et al. Cell factory construction accelerated by genome synthesis and rearrangement. CIESC Journal, 2019, 70(10):3712-3721.
[84] Jia B, Wu Y, Li B Z, et al. Precise control of SCRaMbLE in synthetic haploid and diploid yeast. Nature Communications, 2018, 9:1933.
doi: 10.1038/s41467-018-03084-4
[85] Hochrein L, Mitchell L A, Schulz K, et al. L-SCRaMbLE as a tool for light-controlled Cre-mediated recombination in yeast. Nature Communications, 2018, 9:1931.
doi: 10.1038/s41467-017-02208-6 pmid: 29789561
[86] Luo Z Q, Wang L H, Wang Y, et al. Identifying and characterizing SCRaMbLEd synthetic yeast using ReSCuES. Nature Communications, 2018, 9:1930.
doi: 10.1038/s41467-017-00806-y
[87] Shen M J, Wu Y, Yang K, et al. Heterozygous diploid and interspecies SCRaMbLEing. Nature Communications, 2018, 9(1):1934.
doi: 10.1038/s41467-018-04157-0
[88] Ma L, Li Y X, Chen X Y, et al. SCRaMbLE generates evolved yeasts with increased alkali tolerance. Microbial Cell Factories, 2019, 18(1):52.
doi: 10.1186/s12934-019-1102-4
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