枯草芽胞杆菌蛋白质表达分泌系统发展及展望
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摘要
枯草芽胞杆菌作为革兰阳性模式菌株是基础研究和工业应用的常用宿主细胞。介绍了枯草芽胞杆菌中蛋白合成和分泌过程中的重要步骤及重要调控位点。在枯草芽胞杆菌蛋白表达及分泌系统中,可以针对目标基因在体内的转录、翻译、折叠、转运和菌株改造等方面对表达分泌系统进行优化改良,针对不同的目标蛋白,可进行不同优化模块的组装和拼搭,以达到针对目标蛋白产物定制化地提高产量和分泌量的目的。在未来,随着基因编辑和合成生物技术的发展,菌株改良策略的不断优化,枯草芽胞杆菌将会在工业生产蛋白质制品领域发挥更大的应用价值。
Bacillus subtilis is a common gram-positive model strain and a host cell with great industrial application potential. In this review, the important steps and regulatory sites in protein synthesis and secretion in Bacillus subtilis were introduced. In Bacillus subtilis protein expression and secretion system, the modification of protein expression and secretion system can aim at the transcription of target genes, protein translation, folding, transport and strain optimization improvement. According to different target proteins, the different optimization modules can be assembled, for achieving customization of improving target proteins production, increasing the amount of protein secretion. In the future, accompanying with the further developing of gene editing, synthetic biotechnology and continuous optimization of strain improvement strategy, Bacillus subtilis will play a more important role in protein production.
Bacillus subtilis is a common gram-positive model strain and a host cell with great industrial application potential. In this review, the important steps and regulatory sites in protein synthesis and secretion in Bacillus subtilis were introduced. In Bacillus subtilis protein expression and secretion system, the modification of protein expression and secretion system can aim at the transcription of target genes, protein translation, folding, transport and strain optimization improvement. According to different target proteins, the different optimization modules can be assembled, for achieving customization of improving target proteins production, increasing the amount of protein secretion. In the future, accompanying with the further developing of gene editing, synthetic biotechnology and continuous optimization of strain improvement strategy, Bacillus subtilis will play a more important role in protein production.
引文
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[5] Kunst F, Ogasawara N, Moszer I, et al. The complete genome sequence of the gram-positive bacterium Bacillus subtilis[J]. Nature,1997,390(6657):249-256.
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[12] Phan TT, Nguyen HD, Schumann W. Development of a strong intracellular expression system for Bacillus subtilis by optimizing promoter elements[J]. J Biotechnol,2012,157(1):167-172.
[13] Chen PT, Shaw JF, Chao YP, et al. Construction of chromosomally located T7 expression system for production of heterologous secreted proteins in Bacillus subtilis[J]. J Agric Food Chem,2010,58(9):5392-5399.
[14] Bhavsar AP, Zhao X, Brown ED. Development and characterization of a xylose-dependent system for expression of cloned genes in Bacillus subtilis: conditional complementation of a teichoic acid mutant[J]. Appl Environ Microbiol,2001,67(1):403-410.
[15] Liu SL, Du K. Enhanced expression of an endoglucanase in Bacillus subtilis by using the sucrose-inducible sacB promoter and improved properties of the recombinant enzyme[J]. Protein Expr Purif,2012,83(2):164-168.
[16] Yansura DG, Henner DJ. Use of the Escherichia coli lac repressor and operator to control gene expression in Bacillus subtilis[J]. Proc Natl Acad Sci USA,1984,81(2):439-443.
[17] Ye R, Kim JH, Kim BG, et al. High-level secretory production of intact, biologically active staphylokinase from Bacillus subtilis[J]. Biotechnol Bioeng ,1999,62(1):87-96.
[18] Toymentseva AA, Schrecke K, Sharipova MR, et al. The LIKE system, a novel protein expression toolbox for Bacillus subtilis based on the liaI promoter[J]. Microb Cell Fact,2012,11:143.
[19] Heravi KM, Wenzel M, Altenbuchner J. Regulation of mtl operon promoter of Bacillus subtilis: requirements of its use in expression vectors[J]. Microb Cell Fact,2011,10:83.
[20] Ming YM, Wei ZW, Lin CY, et al. Development of a Bacillus subtilis expression system using the improved Pglv promoter[J]. Microb Cell Fact,2010,9:55.
[21] Phan TT, Schumann W. Development of a glycine-inducible expression system for Bacillus subtilis[J]. J Biotechnol,2007,128(3):486-499.
[22] Yue J, Fu G, Zhang D, et al. A new maltose-inducible high-performance heterologous expression system in Bacillus subtilis[J]. Biotechnol Lett,2017,39(8):1237-1244.
[23] Lee SJ, Pan JG, Park SH, et al. Development of a stationary phase-specific autoinducible expression system in Bacillus subtilis[J]. J Biotechnol,2010,149(1-2):16-20.
[24] Wenzel M, Muller A, Siemann-Herzberg M, et al. Self-inducible Bacillus subtilis expression system for reliable and inexpensive protein production by high-cell-density fermentation[J]. Appl Environ Microbiol,2011,77(18):6419-6425.
[25] Panahi R, Vasheghani-Farahani E, Shojaosadati S, et al. Induction of Bacillus subtilis expression system using environmental stresses and glucose starvation [M]. Ann Microbiol,2014,64:879.
[26] Thuy Le AT, Schumann W. A novel cold-inducible expression system for Bacillus subtilis[J]. Protein Expr Purif,2007,53(2):264-269.
[27] Li W, Li HX, Ji SY, et al. Characterization of two temperature-inducible promoters newly isolated from B. subtilis[J]. Biochem Biophys Res Commun,2007,358(4):1148-1153.
[28] Zhang WW, Gao QR, Yang MM, et al. Assay and characterization of an osmolarity inducible promoter newly isolated from Bacillus subtilis[J]. Mol Biol Rep,2012,39(7):7347-7353.
[29] Paccez JD, Luiz WB, Sbrogio-Almeida ME, et al. Stable episomal expression system under control of a stress inducible promoter enhances the immunogenicity of Bacillus subtilis as a vector for antigen delivery[J]. Vaccine,2006,24(15):2935-2943.
[30] Nijland R, Lindner C, van Hartskamp M, et al. Heterologous production and secretion of Clostridium perfringens beta-toxoid in closely related Gram-positive hosts[J]. J Biotechnol,2007,127(3):361-372.
[31] Jan J, Valle F, Bolivar F, et al. Construction of protein overproducer strains in Bacillus subtilis by an integrative approach[J]. Appl Microbiol Biotechnol,2001,55(1):69-75.
[32] Zhang XZ, Cui ZL, Hong Q, et al. High-level expression and secretion of methyl parathion hydrolase in Bacillus subtilis WB800[J]. Appl Environ Microbiol,2005,71(7):4101-4103.
[33] Yang M, Zhang W, Ji S, et al. Generation of an artificial double promoter for protein expression in Bacillus subtilis through a promoter trap system[J]. PLoS One,2013,8(2):e56321.
[34] Zyprian E, Matzura H. Characterization of signals promoting gene expression on the Staphylococcus aureus plasmid pUB110 and development of a gram-positive expression vector system[J]. Dna,1986,5(3):219-225.
[35] Zhang AL, Liu H, Yang MM, et al. Assay and characterization of a strong promoter element from B. subtilis[J]. Biochem Biophys Res Commun,2007,354(1):90-95.
[36] Hambraeus G, Karhumaa K, Rutberg B. A 5′ stem-loop and ribosome binding but not translation are important for the stability of Bacillus subtilis aprE leader mRNA[J]. Microbiology,2002,148:1795-1803.
[37] Sharp JS, Bechhofer DH. Effect of translational signals on mRNA decay in Bacillus subtilis[J]. J Bacteriol,2003,185(18):5372-5379.
[38] Vellanoweth RL, Rabinowitz JC. The influence of ribosome-binding-site elements on translational efficiency in Bacillus subtilis and Escherichia coli in vivo[J]. Mol Microbiol,1992,6(9):1105-1114.
[39] Phan TT, Nguyen HD, Schumann W. Construction of a 5′-controllable stabilizing element (CoSE) for over-production of heterologous proteins at high levels in Bacillus subtilis[J]. J Biotechnol,2013,168(1):32-39.
[40] Chen J, Gai Y, Fu G, et al. Enhanced extracellular production of alpha-amylase in Bacillus subtilis by optimization of regulatory elements and over-expression of PrsA lipoprotein[J]. Biotechnol Lett,2015,37(4):899-906.
[41] Natale P, Bruser T, Driessen AJ. Sec- and Tat-mediated protein secretion across the bacterial cytoplasmic membrane--distinct translocases and mechanisms[J]. Biochim Biophys Acta,2008,1778(8):1735-1756.
[42] Mu D, Lu J, Qiao M, et al. Heterologous signal peptides-directing secretion of Streptomyces mobaraensis transglutaminase by Bacillus subtilis[J]. Appl Microbiol Biotechnol,2018,102(13):5533-5543.
[43] Guan C, Cui W, Cheng J, et al. Construction of a highly active secretory expression system via an engineered dual promoter and a highly efficient signal peptide in Bacillus subtilis[J]. N Biotechnol,2016,33(3):372-379.
[44] Tsirigotaki A, De Geyter J, Sostaric N, et al. Protein export through the bacterial Sec pathway[J]. Nat Rev Microbiol,2017,15(1):21-36.
[45] Akopian D, Shen K, Zhang X, et al. Signal recognition particle: an essential protein-targeting machine[J]. Annu Rev Biochem,2013,82:693-721.
[46] Collinson I. SecA-a New Twist in the Tale[J]. J Bacteriol,2017,199(2):e00736-16.
[47] Kakeshita H, Kageyama Y, Ara K, et al. Enhanced extracellular production of heterologous proteins in Bacillus subtilis by deleting the C-terminal region of the SecA secretory machinery[J]. Mol Biotechnol,2010,46(3):250-257.
[48] Mulder KC, Bandola J, Schumann W. Construction of an artificial secYEG operon allowing high level secretion of alpha-amylase[J]. Protein Expr Purif,2013,89(1):92-96.
[49] Goosens VJ, van Dijl JM. Twin-Arginine Protein Translocation[J]. Curr Top Microbiol Immunol,2017,404:69-94.
[50] Goosens VJ, Monteferrante CG, van Dijl JM. The Tat system of Gram-positive bacteria[J]. Biochim Biophys Acta,2014,1843(8):1698-1706.
[51] Goosens VJ, Otto A, Glasner C, et al. Novel twin-arginine translocation pathway-dependent phenotypes of Bacillus subtilis unveiled by quantitative proteomics[J]. J Proteome Res,2013,12(2):796-807.
[52] Yang C, Song C, Freudl R, et al. Twin-arginine translocation of methyl parathion hydrolase in Bacillus subtilis[J]. Environ Sci Technol,2010,44(19):7607-7612.
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