代谢工程中途径和菌株改造的几种新技术

doi:10.11949/j.issn.0438-1157.20150641

摘要/Abstract

摘要：

代谢工程是生物学领域重要的发展方向,迄今为止已有20多年的发展历史。通过代谢工程手段对微生物进行遗传改造,可以实现一系列化合物的可持续生产,为能源及环境问题提供了有潜力的解决方案。最近几年代谢工程领域出现了一些最新技术,包括多变量的模块化优化技术、酶集结的支架技术、代谢流量的动态调控技术以及大规模基因编辑技术。本文对这些技术发展及应用进行了总结和介绍。

关键词: 代谢, 生物工程, 合成生物学, 模块化优化, 蛋白支架, 动态调控, 基因编辑

Abstract:

Metabolic engineering is an important development direction in the field of biology. So far it has a history of more than 20 years. Genetic modification of microorganisms by means of metabolic engineering can realize the sustainable production of a series of compounds, providing a potential solution for the energy and environmental problems. In recent years, some new technologies have been developed in the field of metabolic engineering, including the multivariable modular optimization technology, scaffold technology for enzyme assembly, dynamic control of metabolic flux and large-scale genome editing technology. Here we summarized and introduced the development and application of these technologies.

Key words: metabolism, bioengineering, synthetic biology, modular optimization, protein scaffold, dynamic control, genome editing

中图分类号:

Q819

孙新晓, 唐秋雅, 袁其朋. 代谢工程中途径和菌株改造的几种新技术[J]. 化工学报, 2015, 66(8): 2831-2837.

SUN Xinxiao, TANG Qiuya, YUAN Qipeng. Several new technologies for pathway and strain modification by metabolic engineering[J]. CIESC Journal, 2015, 66(8): 2831-2837.

参考文献 34

[1]	Lo T M, Teo W S, Ling H, Chen B, Kang A, Chang M W. Microbial engineering strategies to improve cell viability for biochemical production [J]. Biotechnol. Adv., 2013, 31: 903-914.
[2]	Yadav V G, De Mey M, Lim C G, Ajikumar P K, Stephanopoulos G. The future of metabolic engineering and synthetic biology: towards a systematic practice [J]. Metab. Eng., 2012, 14: 233-241.
[3]	Inokuma K, Liao J C, Okamoto M, Hanai T. Improvement of isopropanol production by metabolically engineered Escherichia coli using gas stripping [J]. J. Biosci. Bioeng., 2010, 110: 696-701.
[4]	Becker J, Zelder O, Hfifner S, Schröder H, Wittmann C. From zero to hero—design-based systems metabolic engineering of Corynebacterium glutamicum for L-lysine production [J]. Metab. Eng., 2011, 13: 159-168.
[5]	Ajikumar P K, Xiao W H, Tyo K E J, Wang Y, Simeon F, Leonard E, Mucha O, Phon T H, Pfeifer B, Stephanopoulos G. Isoprenoid pathway optimization for taxol precursor overproduction in Escherichia coli [J]. Science, 2010, 330: 70-74.
[6]	Xu P, Gu Q, Wang W, Wong L, Bower A G, Collins C H, Koffas M A. Modular optimization of multi-gene pathways for fatty acids production in E. coli [J]. Nat. Commun., 2013, 4: 1409.
[7]	Liu Y, Zhu Y, Li J, Shin H D, Chen R R, Du G, Liu L, Chen J. Modular pathway engineering of Bacillus subtilis for improved N-acetylglucosamine production [J]. Metab. Eng., 2014, 23: 42-52.
[8]	Lin Y, Sun X, Yuan Q, Yan Y. Extending shikimate pathway for the production of muconic acid and its precursor salicylic acid in Escherichia coli [J]. Metab. Eng., 2014, 23: 62-69.
[9]	Wu J, Liu P, Fan Y, Bao H, Du G, Zhou J, Chen J. Multivariate modular metabolic engineering of Escherichia coli to produce resveratrol from L-tyrosine [J]. J. Biotechnol., 2013, 167: 404-411.
[10]	Wu J, Du G, Zhou J, Chen J. Metabolic engineering of Escherichia coli for (2S)-pinocembrin production from glucose by a modular metabolic strategy [J]. Metab. Eng., 2013, 16: 48-55.
[11]	Zhao J, Li Q, Sun T, Zhu X, Xu H, Tang J, Zhang X, Ma Y. Engineering central metabolic modules of Escherichia coli for improving beta-carotene production [J]. Metab. Eng., 2013, 17: 42-50.
[12]	Dai Zhubo, Liu Yi, Huang Luqi, Zhang Xueli. Production of miltiradiene by metabolically engineered Saccharomyces cerevisiae [J]. Biotechnology and Bioengineering, 2012, 109(11): 2845-2853.
[13]	Miles E W. Tryptophan synthase: a multienzyme complex with an intramolecular tunnel [J]. Chem. Rec., 2001, 1: 140-151.
[14]	Smith S, Tsai S C. The type Ⅰ fatty acid and polyketide synthases: a tale of two megasynthases [J]. Nat. Prod. Rep., 2007, 24: 1041-1072.
[15]	Dueber J E, Wu G C, Malmirchegini G R, Moon T S, Petzold C J, Ullal A V, Prather K L, Keasling J D. Synthetic protein scaffolds provide modular control over metabolic flux [J]. Nat. Biotechnol., 2009, 27: 753-759.
[16]	Moon T S, Dueber J E, Shiue E, Prather K L J. Use of modular, synthetic scaffolds for improved production of glucaric acid in engineered E. coli [J]. Metab. Eng., 2010, 12: 298-305.
[17]	Wilner O I, Weizmann Y, Gill R, Lioubashevski O, Freeman R, Willner I. Enzyme cascades activated on topologically programmed DNA scaffolds [J]. Nat. Nanotechnol., 2009, 4: 249-254.
[18]	Delebecque C J, Lindner A B, Silver P A, Aldaye F A. Organization of intracellular reactions with rationally designed RNA assemblies [J]. Science, 2011, 333: 470-474.
[19]	Zhou L, Zuo Z R, Chen X Z, Niu D D, Tian K M, Prior B A, Shen W, Shi G Y, Singh S, Wang Z X. Evaluation of genetic manipulation strategies on D-lactate production by Escherichia coli [J]. Curr. Microbiol., 2011, 62: 981-989.
[20]	Yim H, Haselbeck R, Niu W, Pujol-Baxley C, Burgard A, Boldt J, Khandurina J, Trawick J D, Osterhout R E, Stephen R, Estadilla J, Teisan S, Schreyer H B, Andrae S, Yang T H, Lee S Y, Burk M J, Van Dien S. Metabolic engineering of Escherichia coli for direct production of 1,4-butanediol [J]. Nat. Chem. Biol., 2011, 7: 445-452.
[21]	Williams T C, Averesch N J H, Winter G, Plan M R, Vickers C E, Nielsen L K, Krömer J O. Quorum-sensing linked RNA interference for dynamic metabolic pathway control in Saccharomyces cerevisiae [J]. Metab. Eng., 2015, 29: 124-134.
[22]	Zhou L, Niu D D, Tian K M, Chen X Z, Prior B A, Shen W, Shi G Y, Singh S, Wang Z X. Genetically switched D-lactate production in Escherichia coli [J]. Metab. Eng., 2012, 14: 560-568.
[23]	Soma Y, Tsuruno K, Wada M, Yokota A, Hanai T. Metabolic flux redirection from a central metabolic pathway toward a synthetic pathway using a metabolic toggle switch [J]. Metab. Eng., 2014, 23: 175-184.
[24]	Farmer W R, Liao J C. Improving lycopene production in Escherichia coli by engineering metabolic control [J]. Nat. Biotechnol., 2000, 18: 533-537.
[25]	Xu P, Li L, Zhang F, Stephanopoulos G, Koffas M. Improving fatty acids production by engineering dynamic pathway regulation and metabolic control [J]. Proc. Natl. Acad. Sci. U. S. A., 2014, 111: 11299-11304.
[26]	Urnov F D, Rebar E J, Holmes M C, Zhang H S, Gregory P D. Genome editing with engineered zinc finger nucleases [J]. Nat. Rev. Genet., 2010, 11: 636-646.
[27]	Joung J K, Sander J D. TALENs: a widely applicable technology for targeted genome editing [J]. Nat. Rev. Mol. Cell Biol., 2013, 14: 49-55.
[28]	Bhaya D, Davison M, Barrangou R. CRISPR-Cas systems in bacteria and archaea: versatile small RNAs for adaptive defense and regulation [J]. Annu. Rev. Genet., 2011, 45: 273-297.
[29]	DiCarlo J E, Norville J E, Mali P, Rios X, Aach J, Church G M. Genome engineering in Saccharomyces cerevisiae using CRISPR-Cas systems [J]. Nucleic Acids Res., 2013, 41: 4336-4343.
[30]	Jiang W, Bikard D, Cox D, Zhang F, Marraffini L A. RNA-guided editing of bacterial genomes using CRISPR-Cas systems [J]. Nat. Biotech., 2013, 31: 233-239.
[31]	Jako?iūnas T, Bonde I, Herrgård M, Harrison S J, Kristensen M, Pedersen L E, Jensen M K, Keasling J D. Multiplex metabolic pathway engineering using CRISPR/Cas9 in Saccharomyces cerevisiae [J]. Metab. Eng., 2015, 28: 213-222.
[32]	Qi Lei S, Larson Matthew H, Gilbert Luke A, Doudna Jennifer A, Weissman Jonathan S, Arkin Adam P, Lim Wendell A. Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression [J]. Cell, 152: 1173-1183.
[33]	Cheng A W, Wang H, Yang H, Shi L, Katz Y, Theunissen T W, Rangarajan S, Shivalila C S, Dadon D B, Jaenisch R. Multiplexed activation of endogenous genes by CRISPR-on, an RNA-guided transcriptional activator system [J]. Cell Res., 2013, 23: 1163-1171.
[34]	Gilbert L A, Larson M H, Morsut L, Liu Z, Brar G A, Torres S E, Stern-Ginossar N, Brandman O, Whitehead E H, Doudna J A, Lim W A, Weissman J S, Qi L S. CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes [J]. Cell, 2013, 154: 442-451.