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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2020, Vol. 40 Issue (5): 94-104    DOI: 10.13523/j.cb.1912031
综述     
丝状真菌蛋白表达系统研究进展*
胡益波1,2,**(),皮畅钰1,2,张哲1,2,向柏宇1,2,夏立秋1,2
1 湖南师范大学生命科学学院 淡水鱼类发育生物学国家重点实验室 长沙 410081
2 湖南师范大学生命科学学院 微生物分子生物学湖南省重点实验室 长沙 410081
Recent Advances in Protein Expression System of Filamentous Fungi
HU Yi-bo1,2,**(),PI Chang-yu1,2,ZHANG Zhe1,2,XIANG Bo-yu1,2,XIA Li-qiu1,2
1 State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha 410081, China
2 Hunan Provincial Key Laboratory of Microbial Molecular Biology, College of Life Science, Hunan Normal University, Changsha, 410081, China
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摘要：

丝状真菌以其优秀的表达分泌能力和良好的环境适应能力,使得其在蛋白质表达领域应用越来越广泛。近几十年来,通过诱变、培养优化及遗传改造等手段,使得包含曲霉属、木霉属、青霉属等在内的丝状真菌被开发成高效表达宿主。为促进丝状真菌蛋白表达系统的开发,结合作者的研究工作,对工业上丝状真菌表达宿主、蛋白质表达元件及其改造策略进行综述,并探讨了当前丝状真菌表达系统开发过程中的不足之处,为新型丝状真菌表达系统的研究提供参考和启示。
关键词： 丝状真菌;  表达系统;  蛋白质表达;  宿主;  启动子    
Abstract:

Filamentous fungi, which with excellent protein secretion and environmental adaptability, are widely used in protein expression fields. In recent decades, the expression efficiency of filamentous fungi including Aspergillus sp., Trichoderma sp. and Penicillium sp. has been continuously increased by means of mutagenesis,culture optimization and genetic modification. In order to promote the development of filamentous fungal protein expression system,filamentous fungi expression hosts, protein expression elements and their modification strategies were reviewed . At the same time, the disadvantage in the development of filamentous fungal expression system were discussed to provide references and insights for the study of novel filamentous fungi expression systems.
Key words: Filamentous fungi    Expression system    Protein expression    Host    Promoter
收稿日期: 2019-12-18 出版日期: 2020-06-02
ZTFLH:  Q816  
基金资助: * 国家自然科学青年基金(31700019);湖南省教育厅平台项目(17K057)
通讯作者: 胡益波     E-mail: huyibo@hunnu.edu.cn
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引用本文:

胡益波,皮畅钰,张哲,向柏宇,夏立秋. 丝状真菌蛋白表达系统研究进展*[J]. 中国生物工程杂志, 2020, 40(5): 94-104.

HU Yi-bo,PI Chang-yu,ZHANG Zhe,XIANG Bo-yu,XIA Li-qiu. Recent Advances in Protein Expression System of Filamentous Fungi. China Biotechnology, 2020, 40(5): 94-104.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.1912031    或    https://manu60.magtech.com.cn/biotech/CN/Y2020/V40/I5/94

Promotion type Promoter Source Reference Promoter Source Reference
Constitutive tpiA A. nidulans [47] pki T. reesei [48]
adhA A. nidulans [47] tef1 T. reesei [48]
gpdA A. nidulans [49] pgk1 T. reesei [48]
oliC A. nidulans [49] gpd T. reesei [50]
tef1 A. oryzae [51] cdna1 T. reesei [34]
mbfA A. niger [52] pdc T. reesei [53]
coxA A. niger [52] eno T. reesei [53]
srpB A. niger [52] ubiD P. oxalicum [23]
tvdA A. niger [52] pgmC P. oxalicum [23]
mdhA A. niger [52] aciA P. oxalicum [23]
manB A. niger [52] pcbAB P.chrysogenum [54]
bphA A. niger [55] pcbC P.chrysogenum [56]
rp2 T. reesei [57] SHO1 P.chrysogenum [56]
Conditional alcA A. nidulans [58] cbhI T. reesei [59]
oliC/acuD A. nidulans [49] cbhII T. reesei [60]
alcC A. nidulans [47] xyn2 T. reesei [61]
glaA A. niger [62] egl2 T. reesei [63]
gas A. niger [64] tcu1 T. reesei [65]
pacA A. niger [66] cbhI P. oxalicum [5]
exlA A. awamori [67] xylA P. chrysogenum [68]
thiA A.oryzae [69] ChiI M. thermophila [36]
表1  丝状真菌中常用的启动子
图1  多拷贝启动子增强目标基因转录示意图
图2  利用转录因子——启动子模块增强目标基因转录示意图
图3  人工启动子构建示意图
[1] Ward O P . Production of recombinant proteins by filamentous fungi. Biotechnology Advances, 2012,30(5):1119-1139.
[2] Li D, Tang Y, Lin J , et al. Methods for genetic transformation of filamentous fungi. Microbial Cell Factories, 2017,16(1):168.
[3] te Biesebeke R, Record E, van Biezen N , et al. Branching mutants of Aspergillus oryzae with improved amylase and protease production on solid substrates. Applied Microbiology and Biotechnology, 2005,69(1):44-50.
[4] Demain A L, P Vaishnav . Production of recombinant proteins by microbes and higher organisms. Biotechnology Advances, 2009,27(3):297-306.
[5] Liu G, Zhang L, Qin Y , et al. Long-term strain improvements accumulate mutations in regulatory elements responsible for hyper-production of cellulolytic enzymes. Scientific Reports, 2013,3:1569.
[6] Peterson R, Nevalainen H J M . Trichoderma reesei RUT-C30-thirty years of strain improvement. Microbiology, 2012,158(1):58-68.
[7] Wilson R A, Calvo A M, Chang P K , et al. Characterization of the Aspergillus parasiticus Δ12-desaturase gene: a role for lipid metabolism in the Aspergillus-seed interaction. Microbiology, 2004,150(9):2881-2888.
[8] Withers J M, Swift R J, Wiebe M G , et al. Optimization and stability of glucoamylase production by recombinant strains of Aspergillus niger in chemostat culture. Biotechnology and Bioengineering, 1998,59(4):407-18.
[9] Punt P J, van Biezen N, Conesa A , et al. Filamentous fungi as cell factories for heterologous protein production. Trends in Biotechnology, 2002,20(5):200-206.
[10] Wiebe M G, Karandikar A, Robson G D , et al. Production of tissue plasminogen activator (t-PA) in Aspergillus niger. Biotechnology and Bioengineering, 2001,76(2):164-174.
[11] Nakajima K-i, Asakura T, Maruyama J I , et al. Extracellular production of neoculin, a sweet-tasting heterodimeric protein with taste-modifying activity, by Aspergillus oryzae. Applied and Environmental Microbiology, 2006,72(5):3716-3723.
[12] Merino S T, Cherry J . Progress and challenges in enzyme development for biomass utilization. Advances in Biochemical Engineering-Biotechnology, 2007,108:95-120.
[13] Seiboth B, Ivanova C, Seidl-Seiboth V . Trichoderma reesei: a fungal enzyme producer for cellulosic biofuels, in biofuel production-recent developments and prospects. Rijeka:InTech, 2011: 309-340.
[14] Cherry J R, Fidantsef A L . Directed evolution of industrial enzymes: an update. Current Opinion in Biotechnology, 2003,14(4):438-443.
[15] Zhang X, Xia L . Expression of Talaromyces thermophilus lipase gene in Trichoderma reesei by homologous recombination at the cbh1 locus. Journal of Industrial Microbiology & Biotechnology, 2017,44(3):377-385.
[16] Colabardini C, Valkonen M, Huuskonen A , et al. Expression of two novel beta-glucosidases from Chaetomium atrobrunneum in Trichoderma reesei and characterization of the heterologous protein products. Molecular Biotechnology, 2016,58(12):821-831.
doi: 10.1007/s12033-016-9981-7
[17] Sun N, Qian Y, Wang W , et al. Heterologous expression of Talaromyces emersonii cellobiohydrolase Cel7A in Trichoderma reesei increases the efficiency of corncob residues saccharification. Biotechnology Letter, 2018,40(7):1119-1126.
[18] Fang H, Xia L . High activity cellulase production by recombinant Trichoderma reesei ZU-02 with the enhanced cellobiohydrolase production. Bioresource Technology, 2013,144(complete):693-697.
[19] Fang X, Shen Y, Zhao J , et al. Status and prospect of lignocellulosic bioethanol production in China. Bioresource Technology, 2010,101(13):4814-4819.
[20] Qu Y, Xin Z, Gao P , et al. Cellulase production from spent sulfite liquor and paper-mill waste fiber. Applied Biochemistry and Biotechnology, 1991,28(1):363-368.
[21] Yao G, Li Z, Gao L , et al. Redesigning the regulatory pathway to enhance cellulase production in Penicillium oxalicum. Biotechnology for Biofuels, 2015,8(1):71.
[22] Wang L, Zhao S, Chen X X , et al. Secretory overproduction of a raw starch-degrading glucoamylase in Penicillium oxalicum using strong promoter and signal peptide. Applied Microbiology and Biotechnology, 2018,102(21):9291-9301.
doi: 10.1007/s00253-018-9307-8
[23] Hu Y, Xue H, Liu G , et al. Efficient production and evaluation of lignocellulolytic enzymes using a constitutive protein expression system in Penicillium oxalicum. Journal of Industrial Microbiology and Biotechnology, 2015,42(6):877-887.
[24] Sonderegger C, Galgoczy L, Garrigues S , et al. A Penicillium chrysogenum-based expression system for the production of small, cysteine-rich antifungal proteins for structural and functional analyses. Microbial Cell Factories, 2016,15(1):192.
doi: 10.1186/s12934-016-0586-4
[25] Bukhtojarov F E, Ustinov B B, Salanovich T N , et al. Cellulase complex of the fungus Chrysosporium lucknowense: isolation and characterization of endoglucanases and cellobiohydrolases. Biochemistry (Mosc), 2004,69(5):542-551.
[26] Gusakov A V, Salanovich T N, Antonov A I , et al. Design of highly efficient cellulase mixtures for enzymatic hydrolysis of cellulose. Biotechnology and Bioengineering, 2007,97(5):1028-1038.
doi: 10.1002/(ISSN)1097-0290
[27] Verdoes J C, Punt P J, Burlingame R , et al. A dedicated vector for efficient library construction and high throughput screening in the hyphal fungus Chrysosporium lucknowense. Industrial Biotechnology, 2007,3(1):48-57.
[28] Nakazawa H, Kawai T, Ida N , et al. Construction of a recombinant Trichoderma reesei strain expressing Aspergillus aculeatus β-glucosidase 1 for efficient biomass conversion. Biotechnology and Bioengineering 2012,109(1):92-99.
[29] Zou G, Shi S, Jiang Y , et al. Construction of a cellulase hyper-expression system in Trichoderma reesei by promoter and enzyme engineering. Microbial Cell Factories, 2012,11(1):21.
[30] von Ossowski I, Stahlberg J, Koivula A , et al. Engineering the exo-loop of Trichoderma reesei cellobiohydrolase, Cel7A. A comparison with Phanerochaete chrysosporium Cel7D. Journal of Molecular Biology, 2003,333(4):817-829.
[31] Singh A, Taylor L E, Vander Wall T A , et al. Heterologous protein expression in Hypocrea jecorina: a historical perspective and new developments. Biotechnology Advances, 2015,33(1):142-154.
[32] Paloheimo M, Mantyla A, Kallio J , et al. High-yield production of a bacterial xylanase in the filamentous fungus Trichoderma reesei requires a carrier polypeptide with an intact domain structure. Applied and Environmental Microbiology, 2003,69(12):7073-7082.
doi: 10.1128/AEM.69.12.7073-7082.2003
[33] Linger J G, Taylor L E, Baker J O , et al. A constitutive expression system for glycosyl hydrolase family 7 cellobiohydrolases in Hypocrea jecorina. Biotechnology for Biofuels, 2015,8:45.
[34] Uzbas F, Sezerman U, Hartl L , et al. A homologous production system for Trichoderma reesei secreted proteins in a cellulase-free background. Applied Microbiology and Biotechnology, 2012,93(4):1601-1608.
doi: 10.1007/s00253-011-3674-8
[35] Zhang H, Wang S, Zhang X X , et al. The amyR-deletion strain of Aspergillus niger CICC2462 is a suitable host strain to express secreted protein with a low background. Microbial Cell Factories, 2016,15(1):68.
doi: 10.1186/s12934-016-0463-1
[36] Visser H, Joosten V, Punt P J , et al. Development of a mature fungal technology and production platform for industrial enzymes based on a Myceliophthora thermophila isolate, previously known as Chrysosporium lucknowense C1. Industrial Biotechnology, 2011,7(3):214-223.
[37] Terfruchte M, Wewetzer S, Sarkari P , et al. Tackling destructive proteolysis of unconventionally secreted heterologous proteins in Ustilago maydis. Journal of Industrial Microbiology and Biotechnology, 2018,284:37-51.
[38] Zhang G, Zhu Y, Wei D , et al. Enhanced production of heterologous proteins by the filamentous fungus Trichoderma reesei via disruption of the alkaline serine protease SPW combined with a pH control strategy. Plasmid, 2014,71:16-22.
[39] Landowski C P, Huuskonen A, Wahl R , et al. Enabling low cost biopharmaceuticals: A systematic approach to delete proteases from a well-known protein production host Trichoderma reesei. PLoS One, 2015,10(8):e0134723.
doi: 10.1371/journal.pone.0134723
[40] Landowski C P, Mustalahti E, Wahl R , et al. Enabling low cost biopharmaceuticals: high level interferon alpha-2b production in Trichoderma reesei. Microbial Cell Factories, 2016,15(1):104.
[41] Jin F J, Watanabe T, Juvvadi P R , et al. Double disruption of the proteinase genes, tppA and pepE, increases the production level of human lysozyme by Aspergillus oryzae. Applied Microbiology and Biotechnology, 2007,76(5):1059-1068.
doi: 10.1007/s00253-007-1088-4
[42] Rojas-Sanchez U, Lopez-Calleja A C, Millan-Chiu B E , et al. Enhancing the yield of human erythropoietin in Aspergillus niger by introns and CRISPR-Cas9. Protein Expression and Purification, 2020,168:105570.
[43] Xia C, Li Z, Xu Y , et al. Introduction of heterologous transcription factors and their target genes into Penicillium oxalicum leads to increased lignocellulolytic enzyme production. Applied Microbiology and Biotechnology, 2019,103(6):2675-2687.
[44] Zhang S, Ban A, Ebara N , et al. Self-excising Cre/mutant lox marker recycling system for multiple gene integrations and consecutive gene deletions in Aspergillus oryzae. Journal of Bioscience and Bioengineering, 2017,123(4):403-411.
[45] Schuster M and Kahmann R . CRISPR-Cas9 genome editing approaches in filamentous fungi and oomycetes. Fungal Genetics and Biology, 2019,130:43-53.
doi: 10.1016/j.fgb.2019.04.016
[46] Jorgensen M S, Skovlund D A, Johannesen P F , et al. A novel platform for heterologous gene expression in Trichoderma reesei (Teleomorph Hypocrea jecorina). Microbial Cell Factories, 2014,13(1):33.
[47] Christensen T, Woeldike H, Boel E , et al. High level expression of recombinant genes in Aspergillus oryzae. Bio/technology, 1988,6(12):1419.
[48] Keranen S, Penttila M . Production of recombinant proteins in the filamentous fungus Trichoderma reesei. Current Opinion in Biotechnology, 1995,6(5):534-537.
doi: 10.1016/0958-1669(95)80088-3
[49] De Lucas J R, Gregory S, Turner G . Analysis of the regulation of the Aspergillus nidulans acuD gene, encoding isocitrate lyase, by construction of a hybrid promoter. Molecular Genetics and Genomics, 1994,243(6):654-659.
[50] Penttila M, Nevalainen H, Ratto M , et al. A versatile transformation system for the cellulolytic filamentous fungus Trichoderma reesei. Gene, 1987,61(2):155-164.
[51] Kitamoto N, Matsui J, Kawai Y , et al. Utilization of the TEF1-α gene (TEF1) promoter for expression of polygalacturonase genes, pgaA and pgaB, in Aspergillus oryzae. Applied Microbiology and Biotechnology, 1998,50(1):85-92.
doi: 10.1007/s002530051260
[52] Blumhoff M, Steiger M G, Marx H , et al. Six novel constitutive promoters for metabolic engineering of Aspergillus niger. Applied Microbiology and Biotechnology, 2013,97(1):259-267.
doi: 10.1007/s00253-012-4207-9
[53] Li J, Wang J, Wang S , et al. Achieving efficient protein expression in Trichoderma reesei by using strong constitutive promoters. Microbial Cell Factories, 2012,11:84.
doi: 10.1186/1475-2859-11-84
[54] Nijland J G, Ebbendorf B, Woszczynska M , et al. Nonlinear biosynthetic gene cluster dose effect on penicillin production by Penicillium chrysogenum. Applied and Environmental Microbiology, 2010,76(21):7109-7115.
doi: 10.1128/AEM.01702-10
[55] Antunes M S, Hodges T K, Carpita N C . A benzoate-activated promoter from Aspergillus niger and regulation of its activity. Applied Microbiology and Biotechnology, 2016,100(12):5479-5489.
doi: 10.1007/s00253-016-7373-3
[56] Polli F, Meijrink B, Bovenberg R A L , et al. New promoters for strain engineering of Penicillium chrysogenum. Fungal Genetics and Biology, 2016,89:62-71.
[57] He R, Zhang C, Guo W , et al. Construction of a plasmid for heterologous protein expression with a constitutive promoter in Trichoderma reesei. Plasmid, 2013,70(3):425-429.
[58] Gwynne D I, Buxton F P, Williams S A , et al. Genetically engineered secretion of active human interferon and a bacterial endoglucanase from Aspergillus nidulans. Nature Biotechnology, 1987,5(7):713-719.
[59] Zhang G, Seiboth B, Wen C , et al. A novel carbon source-dependent genetic transformation system for the versatile cell factory Hypocrea jecorina (anamorph Trichoderma reesei). FEMS Microbiology Letters, 2010,303(1):26-32.
doi: 10.1111/fml.2010.303.issue-1
[60] Meng F, Wei D, Wang W . Heterologous protein expression in Trichoderma reesei using the cbhII promoter. Plasmid, 2013,70(2):272-276.
doi: 10.1016/j.plasmid.2013.05.003
[61] Miyauchi S, Te'o V S, Bergquist P L , et al. Expression of a bacterial xylanase in Trichoderma reesei under the egl2 and cbh2 glycosyl hydrolase gene promoters. New Biotechnology, 2013,30(5):523-530.
doi: 10.1016/j.nbt.2013.02.005
[62] Cullen D, Gray G L, Wilson L J , et al. Controlled expression and secretion of bovine chymosin in Aspergillus nidulans. Biotechnology, 1987,5(4):369-376.
[63] Miyauchi S, Te'o V S, Nevalainen K M , et al. Simultaneous expression of the bacterial Dictyoglomus thermophilum xynB gene under three different Trichoderma reesei promoters. New Biotechnology, 2014,31(1):98-103.
doi: 10.1016/j.nbt.2013.08.002
[64] Yin X, Shin H D, Li J , et al. Pgas, a low-ph-induced promoter, as a tool for dynamic control of gene expression for metabolic engineering of Aspergillus niger. Applied and Environmental Microbiology, 2017,83(6):e03222-16.
[65] Lv X, Zheng F, Li C , et al. Characterization of a copper responsive promoter and its mediated overexpression of the xylanase regulator 1 results in an induction-independent production of cellulases in Trichoderma reesei. Biotechnology for Biofuels, 2015,8:67.
doi: 10.1186/s13068-015-0249-4
[66] MacRae W D, Buxton F P, Sibley S , et al. A phosphate-repressible acid phosphatase gene from Aspergillus niger: its cloning, sequencing and transcriptional analysis. Gene, 1988,71(2):339-348.
doi: 10.1016/0378-1119(88)90051-0
[67] Gouka R J, Hessing J G, Punt P J , et al. An expression system based on the promoter region of the Aspergillus awamori 1,4-beta-endoxylanase A gene. Applied Microbiology and Biotechnology, 1996,46(1):28-35.
[68] Díez B, Mellado E, Rodríguez M , et al. The NADP-dependent glutamate dehydrogenase gene from Penicillium chrysogenum and the construction of expression vectors for filamentous fungi. Applied Microbiology and Biotechnology, 1999,52(2):196-207.
doi: 10.1007/s002530051509
[69] Ishida H, Hata Y, Kawato A , et al. Isolation of a novel promoter for efficient protein production in Aspergillus oryzae. Bioscience, Biotechnology and Biochemistry, 2004,68(9):1849-1857.
[70] Zhang J, Zhong Y, Zhao X , et al. Development of the cellulolytic fungus Trichoderma reesei strain with enhanced beta-glucosidase and filter paper activity using strong artificial cellobiohydrolase 1 promoter. Bioresource Technology, 2010,101(24):9815-9818.
doi: 10.1016/j.biortech.2010.07.078
[71] Verdoes J C, Punt P, Van den Hondel C J A M , et al. Molecular genetic strain improvement for the overproduction of fungal proteins by filamentous fungi. Applied Microbiology and Biotechnology 1995,43(2):195-205.
[72] Liu L, Liu J, Qiu R X , et al. Improving heterologous gene expression in Aspergillus niger by introducing multiple copies of protein-binding sequence containing CCAAT to the promoter. Letters in Applied Microbiology, 2010,36(6):358-361.
[73] Zou G, Shi S, Jiang Y , et al. Construction of a cellulase hyper-expression system in Trichoderma reesei by promoter and enzyme engineering. Microbial Cell Factories, 2012,11:21.
[74] Qiu R, Zhu X, Liu L , et al. Detection of a protein, AngCP, which binds specifically to the three upstream regions of glaA gene in A. niger T21. Science in China Series C, 2002,45(5):527-537.
doi: 10.1360/02yc9058
[75] Gressler M, Hortschansky P, Geib E , et al. A new high-performance heterologous fungal expression system based on regulatory elements from the Aspergillus terreus terrein gene cluster. Frontiers in Microbiology, 2015,6:184.
[76] Derntl C, Gudynaite-Savitch L, Calixte S , et al. Mutation of the xylanase regulator 1 causes a glucose blind hydrolase expressing phenotype in industrially used Trichoderma strains. Biotechnology for Biofuels, 2013,6(1):62.
[77] Gao L, Li Z, Xia C , et al. Combining manipulation of transcription factors and overexpression of the target genes to enhance lignocellulolytic enzyme production in Penicillium oxalicum. Biotechnology for Biofuels, 2017,10(1):100.
doi: 10.1186/s13068-017-0783-3
[78] Rantasalo A, Landowski C P, Kuivanen J , et al. A universal gene expression system for fungi. Nucleic Acids Research, 2018,46(18):e111.
[79] Rantasalo A, Vitikainen M, Paasikallio T , et al. Novel genetic tools that enable highly pure protein production in Trichoderma reesei. Scientific Reports, 2019,9(1):5032.
[80] Hinnebusch A G, Ivanov I P, Sonenberg N . Translational control by 5'-untranslated regions of eukaryotic mRNAs. Science, 2016,352(6292):1413-1416.
[81] Koda A, Minetoki T, Ozeki K , et al. Translation efficiency mediated by the 5' untranslated region greatly affects protein production in Aspergillus oryzae. Applied Microbiology and Biotechnology, 2004,66(3):291-296.
doi: 10.1007/s00253-004-1681-8
[82] Koda A, Bogaki T, Minetoki T , et al. 5' Untranslated region of the Hsp12 gene contributes to efficient translation in Aspergillus oryzae. Applied Microbiology and Biotechnology, 2006,70(3):333.
doi: 10.1007/s00253-005-0083-x
[83] Koda A, Bogaki T, Minetoki T , et al. High expression of a synthetic gene encoding potato α-glucan phosphorylase in Aspergillus niger. Journal of Bioscience and Bioengineering, 2005,100(5):531-537.
doi: 10.1263/jbb.100.531
[84] Sun X, Xue X, Li M , et al. Efficient coproduction of mannanase and cellulase by the transformation of a codon-optimized endomannanase gene from Aspergillus niger into Trichoderma reesei. Journal of Agricultural and Food Chemistry, 2017,65(50):11046-11053.
[85] Moralejo F, Watson A, Jeenes D , et al. A defined level of protein disulfide isomerase expression is required for optimal secretion of thaumatin by Aspergillus awamori. Molecular Genetics and Genomics, 2001,266(2):246-253.
[86] Lombrana M, Moralejo F J, Pinto R , et al. Modulation of Aspergillus awamori thaumatin secretion by modification of bipA gene expression. Applied and Environmental Microbiology, 2004,70(9):5145-5152.
[87] Valkonen M, Ward M, Wang H , et al. Improvement of foreign-protein production in Aspergillus niger var. awamori by constitutive induction of the unfolded-protein response. Applied and Environmental Microbiology, 2003,69(12):6979-6986.
[88] Wu Y, Sun X, Xue X , et al. Overexpressing key component genes of the secretion pathway for enhanced secretion of an Aspergillus niger glucose oxidase in Trichoderma reesei. Enzyme and Microbial Technology, 2017,106:83-87.
doi: 10.1016/j.enzmictec.2017.07.007
[89] Yoon J, Aishan T, Maruyama J , et al. Enhanced production and secretion of heterologous proteins by the filamentous fungus Aspergillus oryzae via disruption of vacuolar protein sorting receptor gene Aovps10. Applied and Environmental Microbiology, 2010,76(17):5718-5727.
doi: 10.1128/AEM.03087-09
[90] Zhu L, Maruyama J, Kitamoto K . Further enhanced production of heterologous proteins by double-gene disruption (ΔAosedD ΔAovps10) in a hyper-producing mutant of Aspergillus oryzae. Applied Microbiology and Biotechnology, 2013,97(14):6347-6357.
doi: 10.1007/s00253-013-4795-z
[91] Hoang H D, Maruyama J, Kitamoto K . Modulating endoplasmic reticulum-Golgi cargo receptors for improving secretion of carrier-fused heterologous proteins in the filamentous fungus Aspergillus oryzae. Applied and Environmental Microbiology, 2015,81(2):533-543.
doi: 10.1128/AEM.02133-14
[92] Ward M, Wilson L J, Kodama K H , et al. Improved production of chymosin in Aspergillus by expression as a glucoamylase-chymosin fusion. Bio/technology, 1990,8(5):435-440.
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