基于合成生物技术构建高效生物制造系统的研究进展

doi:10.12211/2096-8280.2021-015

合成生物学 ›› 2021, Vol. 2 ›› Issue (6): 863-875.DOI: 10.12211/2096-8280.2021-015

基于合成生物技术构建高效生物制造系统的研究进展

张晓龙^1,^2,³, 王晨芸^1,^2,³, 刘延峰^1,^2,³, 李江华^2,³, 刘龙^1,^2,³, 堵国成^1,^2,³

^1.江南大学糖化学与生物技术教育部重点实验室，江苏无锡 214122
^2.江南大学未来食品科学中心，江苏无锡 214122
^3.江南大学工业生物技术教育部重点实验室，江苏无锡 214122

收稿日期:2021-02-02 修回日期:2021-08-09 出版日期:2021-12-31 发布日期:2022-01-21
通讯作者: 堵国成
作者简介:张晓龙（1988—），男，博士，助理研究员。研究方向为发酵工程。E-mail：qingshuang0302@163.com|堵国成（1965—），男，博士，教授。研究方向为发酵工程与酶工程。E-mail：gcdu@jiangnan.edu.cn
基金资助:
国家重点研发计划(2018YFA0900300);国家自然科学基金(31972854)

Research progress of constructing efficient biomanufacturing system based on synthetic biotechnology

Xiaolong ZHANG^1,^2,³, Chenyun WANG^1,^2,³, Yanfeng LIU^1,^2,³, Jianghua LI^2,³, Long LIU^1,^2,³, Guocheng DU^1,^2,³

^1.Key Laboratory of Carbohydrate Chemistry and Biotechnology，Jiangnan University，Wuxi 214122，Jiangsu，China
^2.Science Center for Future Foods，Jiangnan University，Wuxi 214122，Jiangsu，China
^3.Key Laboratory of Industrial Biotechnology，Ministry of Education，Jiangnan University，Wuxi 214122，Jiangsu，China

Received:2021-02-02 Revised:2021-08-09 Online:2021-12-31 Published:2022-01-21
Contact: Guocheng DU

摘要/Abstract

摘要：

基于合成生物技术构建绿色高效的生物制造系统是实现可持续化发展的重要途径，该技术的发展应用有望为食品、能源、医药、化工以及畜牧养殖等行业带来革命性的技术变革。本文针对基于合成生物技术构建高效生物制造系统进行系统性的总结与讨论。首先概述了代谢工程、酶工程、辅助系统优化以及发酵过程控制等技术的研究进展；其次，着重对比总结了大肠杆菌、芽孢杆菌属、谷氨棒酸杆菌以及酵母属等典型模式宿主的代谢特性，探究了各微生物制造系统的适用范围。最后，对合成生物技术在构建高效生物制造系统领域中的应用前景进行了展望。精细多元的代谢工程技术、高效简便的酶工程策略以及数字化的微生物系统将是促进高效生物制造系统构建的新引擎与新动力。

关键词: 合成生物技术, 生物制造系统, 典型模式宿主, 代谢工程

Abstract:

Efficient and environmentally friendly biomanufacturing system based on synthetic biotechnology is an important approach to achieve sustainable development. Synthetic biology is expected to bring revolutionary technological breakthroughs in various industries, such as food, pharmacy and chemistry, as well as farming and animal husbandry. In this paper, the latest advances of technologies and strategies in synthetic biology used in the progress of constructing efficient biomanufacturing systems were introduced. Four aspects, namely metabolic regulation of key genes, enzyme engineering, cofactor engineering and fermentation optimization, were discussed. Through these technologies, engineered microorganisms with high robustness and excellent performance were constructed. Secondly, an emphasis was put on the summary of diverse metabolic characteristics of typical model organisms at present. In this part, as many as seven strains were mentioned, such as Escherichia coli, Bacillus subtilis, Bacillus amyloliquefaciens, Bacillus licheniformis, Corynebacterium glutamicum, Pichia pastoris and Saccharomyces cerevisiae. And for each strain, the advantages and disadvantages of different typical model organisms were discussed to clarify the scope of their most suitable products. Escherichia coli is the most intensively studied typical model organism system, making it the preferred expression system for proteins of interest. However, insufficient post-translational processing limits its applications for expressing eukaryotic-derived proteins. Saccharomyces cerevisiae and Pichia pastoris make up for this deficiency. Yeast expression system has significant advantages for the synthesis of natural products from plant, due to the extensive and in-depth research of P450 enzymes, such as the biosynthesis of artemisinin. Lastly, application prospects of synthetic biology in constructing efficient biomanufacturing systems were discussed. With the developments in standard synthetic biology components and data, standard automated work platforms, precise and generally applicable engineering strategies, emerging of machine learning and synthetic biology, it is expected to facilitate efficient biological manufacturing system construction. Precise and various metabolic engineering technology, flexible and convenient enzyme engineering strategies and whole cell microorganism modeling would be the new driving force for efficient biomanufacturing system construction.

Key words: synthetic biotechnology, biomanufacturing systems, typical model microorganisms, metabolic engineering

中图分类号:

Q815

张晓龙, 王晨芸, 刘延峰, 李江华, 刘龙, 堵国成. 基于合成生物技术构建高效生物制造系统的研究进展[J]. 合成生物学, 2021, 2(6): 863-875.

Xiaolong ZHANG, Chenyun WANG, Yanfeng LIU, Jianghua LI, Long LIU, Guocheng DU. Research progress of constructing efficient biomanufacturing system based on synthetic biotechnology[J]. Synthetic Biology Journal, 2021, 2(6): 863-875.

参考文献 105

1	SHEN X L, WANG J, LI C Y, et al. Dynamic gene expression engineering as a tool in pathway engineering[J]. Current Opinion in Biotechnology, 2019, 59: 122-129.
2	WU Y K, CHEN T C, LIU Y F, et al. Design of a programmable biosensor-CRISPRi genetic circuits for dynamic and autonomous dual-control of metabolic flux in Bacillus subtilis[J]. Nucleic Acids Research, 2020, 48(2): 996-1009.
3	SANDER T, FARKE N, DIEHL C, et al. Allosteric feedback inhibition enables robust amino acid biosynthesis in E. coli by enforcing enzyme overabundance[J]. Cell Systems, 2019, 8(1): 66-75.e8.
4	陈修来, 刘佳, 罗秋玲, 等. 微生物辅因子平衡的代谢调控[J]. 生物工程学报, 2017, 33(1): 16-26.
	CHEN X L, LIU J, LUO Q L, et al. Manipulation of cofactor balance in microorganisms[J]. Chinese Journal of Biotechnology, 2017, 33(1): 16-26.
5	GU Y, LÜ X Q, LIU Y F, et al. Synthetic redesign of central carbon and redox metabolism for high yield production of N-acetylglucosamine in Bacillus subtilis[J]. Metabolic Engineering, 2019, 51: 59-69.
6	KIM Y E, HIPP M S, BRACHER A, et al. Molecular chaperone functions in protein folding and proteostasis[J]. Annual Review of Biochemistry, 2013, 82: 323-355.
7	LIANG C N, ZHANG X X, WU J Y, et al. Dynamic control of toxic natural product biosynthesis by an artificial regulatory circuit[J]. Metabolic Engineering, 2020, 57: 239-246.
8	POLKA J K, HAYS S G, SILVER P A. Building spatial synthetic biology with compartments, scaffolds, and communities[J]. Cold Spring Harbor Perspectives in Biology, 2016, 8(8): a024018.
9	WANG Y, HU L T, HUANG H, et al. Eliminating the capsule-like layer to promote glucose uptake for hyaluronan production by engineered Corynebacterium glutamicum[J]. Nature Communications, 2020, 11(1): 3120.
10	陈坚, 刘立明, 堵国成. 发酵过程优化原理与技术[M].北京:化学工业出版社, 2009: 5-14.
	CHEN J, LIU L M, DU G C. Principle and technology of fermentation optimization[M]. Beijing: Chemical Industry Press, 2009: 5-14.
11	GOPAL G J, KUMAR A. Strategies for the production of recombinant protein in Escherichia coli[J]. The Protein Journal, 2013, 32(6): 419-425.
12	TERPE K. Overview of bacterial expression systems for heterologous protein production: from molecular and biochemical fundamentals to commercial systems[J]. Applied Microbiology and Biotechnology, 2006, 72(2): 211-222.
13	TERPE K. Overview of tag protein fusions: from molecular and biochemical fundamentals to commercial systems[J]. Applied Microbiology and Biotechnology, 2003, 60(5): 523-533.
14	ROSANO G L, CECCARELLI E A. Recombinant protein expression in Escherichia coli: advances and challenges[J]. Frontiers in Microbiology, 2014, 5:172.
15	SCHLEIF R. AraC protein, regulation of the L-arabinose operon in Escherichia coli, and the light switch mechanism of AraC action[J]. FEMS Microbiology Reviews, 2010, 34(5): 779-796.
16	QING G L, MA L C, KHORCHID A, et al. Cold-shock induced high-yield protein production in Escherichia coli[J]. Nature Biotechnology, 2004, 22(7): 877-882.
17	WANG X, HAN J N, ZHANG X, et al. Reversible thermal regulation for bifunctional dynamic control of gene expression in Escherichia coli[J]. Nature Communications, 2021, 12(1): 1411.
18	COSTA S J, ALMEIDA A, CASTRO A, et al. The novel Fh8 and H fusion partners for soluble protein expression in Escherichia coli: a comparison with the traditional gene fusion technology[J]. Applied Microbiology and Biotechnology, 2013, 97(15): 6779-6791.
19	BANKI M R, FENG L, WOOD D W. Simple bioseparations using self-cleaving elastin-like polypeptide tags[J]. Nature Methods, 2005, 2(9): 659-661.
20	KAPUST R B, TÖZSÉR J, COPELAND T D, et al. The P1′ specificity of tobacco etch virus protease[J]. Biochemical and Biophysical Research Communications, 2002, 294(5): 949-955.
21	CHOI J H, LEE S Y. Secretory and extracellular production of recombinant proteins using Escherichia coli[J]. Applied Microbiology and Biotechnology, 2004, 64(5):625-635.
22	SCHIERLE C F, BERKMEN M, HUBER D, et al. The DsbA signal sequence directs efficient, cotranslational export of passenger proteins to the Escherichia coli periplasm via the signal recognition particle pathway[J]. Journal of Bacteriology, 2003, 185(19): 5706-5713.
23	SOARES C R J, GOMIDE F I C, UEDA E K M, et al. Periplasmic expression of human growth hormone via plasmid vectors containing the λPL promoter: use of HPLC for product quantification[J]. Protein Engineering, Design and Selection, 2003, 16(12): 1131-1138.
24	MESSENS J, COLLET J F. Pathways of disulfide bond formation in Escherichia coli[J]. The International Journal of Biochemistry & Cell Biology, 2006, 38(7): 1050-1062.
25	NISHIHARA K, KANEMORI M, YANAGI H, et al. Overexpression of trigger factor prevents aggregation of recombinant proteins in Escherichia coli[J]. Applied and Environmental Microbiology, 2000, 66(3): 884-889.
26	FERRER M, LÜNSDORF H, CHERNIKOVA T N, et al. Functional consequences of single: double ring transitions in chaperonins: life in the cold[J]. Molecular Microbiology, 2004, 53(1): 167-182.
27	LUEKING A, HOLZ C, GOTTHOLD C, et al. A system for dual protein expression in Pichia pastoris and Escherichia coli[J]. Protein Expression and Purification, 2000, 20(3): 372-378.
28	STEWART E J, ÅSLUND F, BECKWITH J. Disulfide bond formation in the Escherichia coli cytoplasm: an in vivo role reversal for the thioredoxins[J]. The EMBO Journal, 1998, 17(19):5543-5550.
29	KIM K, CHOE D, LEE D-H, et al. Engineering biology to construct microbial chassis for the production of difficult-to-express proteins[J]. International Journal of Molecular Sciences, 2020, 21(3): 990.
30	FAULKNER M J, VEERAVALLI K, GON S, et al. Functional plasticity of a peroxidase allows evolution of diverse disulfide-reducing pathways[J]. Proceedings of the National Academy of Sciences of the United States of America, 2008, 105(18): 6735-6740.
31	ZELIĆ B, GOSTOVIĆ S, VUORILEHTO K, et al. Process strategies to enhance pyruvate production with recombinant Escherichia coli: from repetitive fed-batch to in situ product recovery with fully integrated electrodialysis[J]. Biotechnology and Bioengineering, 2004, 85(6): 638-646.
32	YANG M H, ZHANG X. Construction of pyruvate producing strain with intact pyruvate dehydrogenase and genome-wide transcription analysis[J]. World Journal of Microbiology and Biotechnology, 2017, 33(3): 59.
33	MATSUMOTO T, TANAKA T, KONDO A. Engineering metabolic pathways in Escherichia coli for constructing a "microbial chassis" for biochemical production[J]. Bioresource Technology, 2017, 245: 1362-1368.
34	KRIVORUCHKO A, ZHANG Y M, SIEWERS V, et al. Microbial acetyl-CoA metabolism and metabolic engineering[J]. Metabolic Engineering, 2015, 28: 28-42.
35	HUANG J F, LIU Z Q, JIN L Q, et al. Metabolic engineering of Escherichia coli for microbial production of L-methionine[J]. Biotechnology and Bioengineering, 2017, 114(4): 843-851.
36	YANG P, WANG J, PANG Q X, et al. Pathway optimization and key enzyme evolution of N-acetylneuraminate biosynthesis using an in vivo aptazyme-based biosensor[J]. Metabolic Engineering, 2017, 43(A): 21-28.
37	YE L J, ZHANG C Z, BI C H, et al. Combinatory optimization of chromosomal integrated mevalonate pathway for β-carotene production in Escherichia coli[J]. Microbial Cell Factories, 2016, 15(1): 202.
38	ALONSO-GUTIERREZ J, CHAN R, BATTH T S, et al. Metabolic engineering of Escherichia coli for limonene and perillyl alcohol production[J]. Metabolic Engineering, 2013, 19: 33-41.
39	ZHOU L, DING Q, JIANG G Z, et al. Chromosome engineering of Escherichia coli for constitutive production of salvianic acid A[J]. Microbial Cell Factories, 2017, 16(1): 84.
40	SCHALLMEY M, SINGH A, WARD O P. Developments in the use of Bacillus species for industrial production[J]. Canadian Journal of Microbiology, 2004, 50(1): 1-17.
41	PETSCH D, ANSPACH F B. Endotoxin removal from protein solutions[J]. Journal of Biotechnology, 2000, 76(2/3): 97-119.
42	SHI T, WANG Y C, WANG Z W, et al. Deregulation of purine pathway in Bacillus subtilis and its use in riboflavin biosynthesis[J]. Microbial Cell Factories, 2014, 13(1): 101.
43	JIN P, KANG Z, YUAN P H, et al. Production of specific-molecular-weight hyaluronan by metabolically engineered Bacillus subtilis 168[J]. Metabolic Engineering, 2016, 35: 21-30.
44	GU Y, XU X H, WU Y K, et al. Advances and prospects of Bacillus subtilis cellular factories: from rational design to industrial applications[J]. Metabolic Engineering, 2018, 50: 109-121.
45	SAITO N. A thermophilic extracellular α-amylase from Bacillus licheniformis[J]. Archives of Biochemistry and Biophysics, 1973, 155(2): 290-298.
46	MACHIUS M, DECLERCK N, HUBER R, et al. Kinetic stabilization of Bacillus licheniformisα-amylase through introduction of hydrophobic residues at the surface[J]. Journal of Biological Chemistry, 2003, 278(13): 11546-11553.
47	SELLAMI-KAMOUN A, HADDAR A, E-H ALI N, et al. Stability of thermostable alkaline protease from Bacillus licheniformis RP1 in commercial solid laundry detergent formulations[J]. Microbiological Research, 2008, 163(3): 299-306.
48	KALIMUTHU K, BABU R S, VENKATARAMAN D, et al. Biosynthesis of silver nanocrystals by Bacillus licheniformis[J]. Colloids and Surfaces B: Biointerfaces, 2008, 65(1): 150-153.
49	KALISHWARALAL K, DEEPAK V, RAMKUMARPANDIAN S, et al. Extracellular biosynthesis of silver nanoparticles by the culture supernatant of Bacillus licheniformis[J]. Materials Letters, 2008, 62(29): 4411-4413.
50	SHIH I L, VAN Y T, YEH L C, et al. Production of a biopolymer flocculant from Bacillus licheniformis and its flocculation properties[J]. Bioresource Technology, 2001, 78(3): 267-272.
51	CAO M F, FENG J, SIRISANSANEEYAKUL S, et al. Genetic and metabolic engineering for microbial production of poly-γ-glutamic acid[J]. Biotechnology Advances, 2018, 36(5):1424-1433.
52	QIU Y M, ZHANG J Y, LI L, et al. Engineering Bacillus licheniformis for the production of meso-2,3-butanediol[J]. Biotechnology for Biofuels, 2016, 9(1): 117.
53	QI G F, KANG Y F, LI L, et al. Deletion of meso-2,3-butanediol dehydrogenase gene budC for enhanced D-2,3-butanediol production in Bacillus licheniformis[J]. Biotechnology for Biofuels, 2014, 7(1): 16.
54	VEITH B, HERZBERG C, STECKEL S, et al. The complete genome sequence of Bacillus licheniformis DSM13, an organism with great industrial potential[J]. Journal of Molecular Microbiology and Biotechnology, 2004, 7(4): 204-211.
55	ZHOU C X, LIU H, YUAN F Y, et al. Development and application of a CRISPR/Cas9 system for Bacillus licheniformis genome editing[J]. International Journal of Biological Macromolecules, 2019, 122: 329-337.
56	ZHAN Y Y, XU Y, ZHENG P L, et al. Establishment and application of multiplexed CRISPR interference system in Bacillus licheniformis[J]. Applied Microbiology and Biotechnology, 2020, 104(1): 391-403.
57	WANG H, YANG L, PING Y H, et al. Engineering of a Bacillus amyloliquefaciens strain with high neutral protease producing capacity and optimization of its fermentation conditions[J]. PLoS One, 2016, 11(1): e0146373.
58	SHA Y Y, HUANG Y Y, ZHU Y F, et al. Efficient biosynthesis of low-molecular-weight poly-γ-glutamic acid based on stereochemistry regulation in Bacillus amyloliquefaciens[J]. ACS Synthetic Biology, 2020, 9(6): 1395-1405.
59	ZHANG F, HUO K Y, SONG X Y, et al. Engineering of a genome-reduced strain Bacillus amyloliquefaciens for enhancing surfactin production[J]. Microbial Cell Factories, 2020, 19(1): 223.
60	YANG N, WU Q, XU Y. Fe nanoparticles enhanced surfactin production in Bacillus amyloliquefaciens[J]. ACS Omega, 2020, 5(12): 6321-6329.
61	GU Y Y, ZHENG J Y, FENG J, et al. Improvement of levan production in Bacillus amyloliquefaciens through metabolic optimization of regulatory elements[J]. Applied Microbiology and Biotechnology, 2017, 101(10): 4163-4174.
62	JIANG C, RUAN L Y, WEI X T, et al. Enhancement of S-adenosylmethionine production by deleting thrB gene and overexpressing SAM2 gene in Bacillus amyloliquefaciens[J]. Biotechnology Letters, 2020, 42(11): 2293-2298.
63	SAMUEL M S, JOSE S, SELVARAJAN E, et al. Biosynthesized silver nanoparticles using Bacillus amyloliquefaciens; Application for cytotoxicity effect on A549 cell line and photocatalytic degradation of p-nitrophenol[J]. Journal of Photochemistry and Photobiology B: Biology, 2020, 202: 111642.
64	INUI M, KAWAGUCHI H, MURAKAMI S, et al. Metabolic engineering of Corynebacterium glutamicum for fuel ethanol production under oxygen-deprivation conditions[J]. Journal of Molecular Microbiology and Biotechnology, 2004, 8(4): 243-254.
65	SASAKI M, JOJIMA T, KAWAGUCHI H, et al. Engineering of pentose transport in Corynebacterium glutamicum to improve simultaneous utilization of mixed sugars[J]. Applied Microbiology and Biotechnology, 2009, 85(1): 105-115.
66	KITADE Y, HASHIMOTO R, SUDA M, et al. Production of 4-hydroxybenzoic acid by an aerobic growth-arrested bioprocess using metabolically engineered Corynebacterium glutamicum[J]. Applied and Environmental Microbiology, 2018, 84(6).
67	KUBOTA T, WATANABE A, SUDA M, et al. Production of para-aminobenzoate by genetically engineered Corynebacterium glutamicum and non-biological formation of an N-glucosyl byproduct[J]. Metabolic Engineering, 2016, 38: 322-330.
68	CHOI J W, JEON E J, JEONG K J. Recent advances in engineering Corynebacterium glutamicum for utilization of hemicellulosic biomass[J]. Current Opinion in Biotechnology, 2019, 57: 17-24.
69	JORGE J M P, PÉREZ-GARCÍA F, WENDISCH V F. A new metabolic route for the fermentative production of 5-aminovalerate from glucose and alternative carbon sources[J]. Bioresource Technology, 2017, 245(B): 1701-1709.
70	BARITUGO K A, KIM H T, DAVID Y, et al. Metabolic engineering of Corynebacterium glutamicum for fermentative production of chemicals in biorefinery[J]. Applied Microbiology and Biotechnology, 2018, 102(9):3915-3937.
71	SCHÄFER A, TAUCH A, JÄGER W, et al. Small mobilizable multi-purpose cloning vectors derived from the Escherichia coli plasmids pK18 and pK19: selection of defined deletions in the chromosome of Corynebacterium glutamicum[J]. Gene, 1994, 145(1): 69-73.
72	SUZUKI N, NONAKA H, TSUGE Y, et al. New multiple-deletion method for the Corynebacterium glutamicum genome, using a mutant lox sequence[J]. Applied and Environmental Microbiology, 2005, 71(12): 8472-8480.
73	WANG Y, LIU Y, LIU J, et al. MACBETH: Multiplex automated Corynebacterium glutamicum base editing method[J]. Metabolic Engineering, 2018, 47: 200-210.
74	HEIDER S A E, WENDISCH V F. Engineering microbial cell factories: metabolic engineering of Corynebacterium glutamicum with a focus on non-natural products[J]. Biotechnology Journal, 2015, 10(8): 1170-1184.
75	BELL S P, LABIB K. Chromosome duplication in Saccharomyces cerevisiae[J]. Genetics, 2016, 203(3): 1027-1067.
76	ZHANG W P, DU G C, ZHOU J W, et al. Regulation of sensing, transportation, and catabolism of nitrogen sources in Saccharomyces cerevisiae[J]. Microbiology and Molecular Biology Reviews, 2018, 82(1): e00040-17.
77	LAUN P, PICHOVA A, MADEO F, et al. Aged mother cells of Saccharomyces cerevisiae show markers of oxidative stress and apoptosis[J]. Molecular Microbiology, 2001, 39(5): 1166-1173.
78	HO Y, GRUHLER A, HEILBUT A, et al. Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry[J]. Nature, 2002, 415(6868): 180-183.
79	UETZ P, GIOT L, CAGNEY G, et al. A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae[J]. Nature, 2000, 403(6770): 623-627.
80	KROGAN N J, CAGNEY G, YU H Y, et al. Global landscape of protein complexes in the yeast Saccharomyces cerevisiae[J]. Nature, 2006, 440(7084): 637-643.
81	NEIMAN A M. Ascospore formation in the yeast Saccharomyces cerevisiae[J]. Microbiology and Molecular Biology Reviews, 2005, 69(4): 565-584.
82	LEVIN D E. Cell wall integrity signaling in Saccharomyces cerevisiae[J]. Microbiology and Molecular Biology Reviews, 2005, 69(2): 262-291.
83	YAMANISHI M, ITO Y, KINTAKA R, et al. A genome-wide activity assessment of terminator regions in Saccharomyces cerevisiae provides a ''terminatome'' toolbox[J]. ACS Synthetic Biology, 2013, 2(6): 337-347.
84	TEIXEIRA M C, MONTEIRO P T, PALMA M, et al. YEASTRACT: an upgraded database for the analysis of transcription regulatory networks in Saccharomyces cerevisiae[J]. Nucleic Acids Research, 2018, 46(D1): D348-D353.
85	BALAKRISHNAN R, PARK J, KARRA K, et al. YeastMine—an integrated data warehouse for Saccharomyces cerevisiae data as a multipurpose tool-kit[J]. Database, 2012, 2012: bar062.
86	SHAO Z Y, ZHAO H, ZHAO H M. DNA assembler, an in vivo genetic method for rapid construction of biochemical pathways[J]. Nucleic Acids Research, 2009, 37(2): e16-e16.
87	KUIJPERS N G, SOLIS-ESCALANTE D, BOSMAN L, et al. A versatile, efficient strategy for assembly of multi-fragment expression vectors in Saccharomyces cerevisiae using 60 bp synthetic recombination sequences[J]. Microbial Cell Factories, 2013, 12: 47.
88	HONG K K, NIELSEN J. Metabolic engineering of Saccharomyces cerevisiae: a key cell factory platform for future biorefineries[J]. Cellular and Molecular Life Sciences, 2012, 69(16): 2671-2690.
89	KAYIKCI Ö, NIELSEN J. Glucose repression in Saccharomyces cerevisiae[J]. FEMS Yeast Research, 2015, 15(6): fov068.
90	HOU J, QIU C X, SHEN Y, et al. Engineering of Saccharomyces cerevisiae for the efficient co-utilization of glucose and xylose[J]. FEMS Yeast Research, 2017, 17(4): fox034.
91	KOZAK B U, ROSSUM H M VAN, LUTTIK M A H, et al. Engineering acetyl coenzyme A supply: functional expression of a bacterial pyruvate dehydrogenase complex in the cytosol of Saccharomyces cerevisiae[J]. mBio, 2014, 5(5): e01696-e01614.
92	JIANG G Z, YAO M D, WANG Y, et al. Manipulation of GES and ERG20 for geraniol overproduction in Saccharomyces cerevisiae[J]. Metabolic Engineering, 2017, 41: 57-66.
93	CHENG S, LIU X, JIANG G Z, et al. Orthogonal engineering of biosynthetic pathway for efficient production of limonene in Saccharomyces cerevisiae[J]. ACS Synthetic Biology, 2019, 8(5): 968-975.
94	DAI Z B, LIU Y, ZHANG X N, et al. Metabolic engineering of Saccharomyces cerevisiae for production of ginsenosides[J]. Metabolic Engineering, 2013, 20: 146-156.
95	PADDON C J, WESTFALL P J, PITERA D J, et al. High-level semi-synthetic production of the potent antimalarial artemisinin[J]. Nature, 2013, 496(7446): 528-532.
96	LUO X, REITER M A, D'ESPAUX L, et al. Complete biosynthesis of cannabinoids and their unnatural analogues in yeast[J]. Nature, 2019, 567(7746): 123-126.
97	GOTTARDI M, REIFENRATH M, BOLES E, et al. Pathway engineering for the production of heterologous aromatic chemicals and their derivatives in Saccharomyces cerevisiae: bioconversion from glucose[J]. FEMS Yeast Research, 2017, 17(4): fox035.
98	KRIVORUCHKO A, NIELSEN J. Production of natural products through metabolic engineering of Saccharomyces cerevisiae[J]. Current Opinion in Biotechnology, 2015, 35: 7-15.
99	LUTTIK M AH, VURALHAN Z, SUIR E, et al. Alleviation of feedback inhibition in Saccharomyces cerevisiae aromatic amino acid biosynthesis: quantification of metabolic impact[J]. Metabolic Engineering, 2008, 10(3/4): 141-153.
100	DEVER T E, KINZY T G, PAVITT G D. Mechanism and regulation of protein synthesis in Saccharomyces cerevisiae[J]. Genetics, 2016, 203(1):65-107.
101	RASALA B A, MAYFIELD S P. Photosynthetic biomanufacturing in green algae; production of recombinant proteins for industrial, nutritional, and medical uses[J]. Photosynthesis Research, 2015, 123(3):227-239.
102	DE SCHUTTER K, LIN Y C, TIELS P, et al. Genome sequence of the recombinant protein production host Pichia pastoris[J]. Nature Biotechnology, 2009, 27(6): 561-566.
103	SCHWARZHANS J P, LUTTERMANN T, GEIER M, et al. Towards systems metabolic engineering in Pichia pastoris[J]. Biotechnology Advances, 2017, 35(6): 681-710.
104	韩明哲, 陈为刚, 宋理富, 等. DNA信息存储: 生命系统与信息系统的桥梁[J]. 合成生物学, 2021, 2(3): 309-322.
	HAN M Z, CHEN W G, SONG L F, et al. DNA information storage: bridging biological and digital world[J]. Synthetic Biology Journal, 2021, 2(3): 309-322.
105	张媛媛, 曾艳, 王钦宏. 合成生物制造进展[J]. 合成生物学, 2021, 2(2): 145-160.
	ZHANG Y Y, ZENG Y, WANG Q H. Advances in synthetic biomanufacturing[J]. Synthetic Biology Journal, 2021, 2(2): 145-160.

[1]	陈永灿, 司同, 张建志. 自动化合成生物技术在DNA组装与微生物底盘操作中的应用[J]. 合成生物学, 2023, 4(5): 857-876.
[2]	程真真, 张健, 高聪, 刘立明, 陈修来. 代谢工程改造微生物利用甲酸研究进展[J]. 合成生物学, 2023, 4(4): 756-778.
[3]	刘家宇, 杨智晗, 杨蕾, 朱丽英, 朱政明, 江凌. 合成生物技术驱动酪丁酸梭菌细胞工厂开发的研究进展[J]. 合成生物学, 2022, 3(6): 1174-1200.
[4]	郭姝媛, 吴良焕, 刘香健, 王博, 于涛. 微生物中一碳代谢网络构建的进展与挑战[J]. 合成生物学, 2022, 3(1): 116-137.
[5]	陈久洲, 王钰, 蒲伟, 郑平, 孙际宾. 5-氨基乙酰丙酸生物合成技术的发展及展望[J]. 合成生物学, 2021, 2(6): 1000-1016.
[6]	汪庆卓, 宋萍, 黄和. 合成生物技术驱动天然的真核油脂细胞工厂开发[J]. 合成生物学, 2021, 2(6): 920-941.
[7]	严伟, 高豪, 蒋羽佳, 钱秀娟, 周杰, 董维亮, 章文明, 信丰学, 姜岷. 2-苯乙醇生物合成的研究进展[J]. 合成生物学, 2021, 2(6): 1030-1045.
[8]	郭亮, 高聪, 柳亚迪, 陈修来, 刘立明. 大肠杆菌生产饲用氨基酸的研究进展[J]. 合成生物学, 2021, 2(6): 964-981.
[9]	曹晨凯, 李佳隆, 张科春. 人工代谢途径合成有机醇有机酸的研究进展[J]. 合成生物学, 2021, 2(6): 902-919.
[10]	高虎涛, 王佳, 孙新晓, 申晓林, 袁其朋. 在大肠杆菌中从头生物合成3-苯丙醇[J]. 合成生物学, 2021, 2(6): 1046-1060.
[11]	林芝, 胡致伟, 瞿旭东, 林双君. 苄基异喹啉类生物碱的微生物合成研究进展及挑战[J]. 合成生物学, 2021, 2(5): 716-733.
[12]	刘裕, 韦惠玲, 刘骥翔, 王少杰, 苏海佳. 人工多菌体系的设计与构建：合成生物学研究新前沿[J]. 合成生物学, 2021, 2(4): 635-650.
[13]	徐鹏. 纪念王义翘教授：解脂耶氏酵母替代植物油脂的技术瓶颈及展望[J]. 合成生物学, 2021, 2(4): 509-527.
[14]	袁姚梦, 邢新会, 张翀. 微生物细胞工厂的设计构建：从诱变育种到全基因组定制化创制[J]. 合成生物学, 2020, 1(6): 656-673.
[15]	于勇, 朱欣娜, 张学礼. 大宗化学品细胞工厂的构建与应用[J]. 合成生物学, 2020, 1(6): 674-684.

基于合成生物技术构建高效生物制造系统的研究进展

Research progress of constructing efficient biomanufacturing system based on synthetic biotechnology

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献 105

相关文章 15

编辑推荐

Metrics

本文评价