大宗化学品细胞工厂的构建与应用

于勇; 朱欣娜; 张学礼

doi:10.12211/2096-8280.2020-049

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大宗化学品细胞工厂的构建与应用

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- 大宗化学品细胞工厂的构建与应用
- Construction and application of microbial cell factories for production of bulk chemicals
- 合成生物学 2020年1卷第6期页码：674-684
- 作者机构：
  
  中国科学院天津工业生物技术研究所，天津　300308
- 作者简介：
  
  [ "于勇（1992—），男，博士，博士后。研究方向为代谢工程、合成生物学。E-mail：yu_yong@tib.cas.cn" ]
  [ "朱欣娜（1975—），女，博士，副研究员。研究方向为代谢工程、合成生物学。E-mail：zhu_xn@tib.cas.cn" ]
  [ "张学礼（1981—），男，博士，研究员。研究方向为代谢工程、合成生物学。E-mail：zhang_xl@tib.cas.cn" ]
- 基金信息：
  
  国家重点研发计划(2019YFA0904900)
- DOI：10.12211/2096-8280.2020-049
  中图分类号： Q81
- 收稿：2020-04-16，
  
  修回：2020-09-25，
  
  纸质出版：2020-12-31
- 稿件说明：
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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

YU Yong, ZHU Xinna, ZHANG Xueli. Construction and application of microbial cell factories for production of bulk chemicals[J]. Synthetic Biology Journal, 2020, 1(6): 674-684
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 DOI： 10.12211/2096-8280.2020-049.

YU Yong, ZHU Xinna, ZHANG Xueli. Construction and application of microbial cell factories for production of bulk chemicals[J]. Synthetic Biology Journal, 2020, 1(6): 674-684 DOI： 10.12211/2096-8280.2020-049.

摘要

随着合成生物学技术的发展，越来越多的大宗化学品可通过微生物细胞工厂发酵生产，为摆脱石油资源依赖、节能减排提供了可能。本文首先介绍了细胞工厂构建所需的关键技术，包括基因组编辑技术、多基因同时调控技术、蛋白骨架技术、基因动态调控技术、高通量筛选技术。随后结合丁二酸细胞工厂这一具体案例，从物质代谢、能量代谢及细胞生理代谢三方面阐述了如何解析微生物高效合成化学品的代谢调控机制，为高效细胞工厂创建奠定理论基础。并对近年来成功构建的大宗化学品细胞工厂作了举例介绍，包括L-丙氨酸、L-甲硫氨酸、丁二酸、D-乳酸、丙二酸、L-苹果酸、戊二酸、己二酸、1，3-丙二醇、1，4-丁二醇和异丁醇等。未来，进一步增加原料利用效率和拓宽产物范围是微生物细胞工厂的发展方向，但新酶设计与改造是限制代谢途径设计的主要瓶颈。相信随着研究的深入，微生物细胞工厂将在替代化学法生产大宗化学品方面有更广泛的应用。

Abstract

With the development of synthetic biology

more and more bulk chemicals can be produced through microbial cell factories

which can avoid the dependence on petroleum resources and decrease energy cost and pollution. In this review

the key technologies for construction of microbial cell factories were firstly introduced

including genome editing

simultaneous modulation of multiple genes

protein scaffold

gene dynamic modulation and high throughput screening technologies. How to characterize the metabolic regulation mechanisms for efficient production of chemicals was then introduced in three aspects: carbon metabolism

energy metabolism and physiological metabolism

and succinate cell factory was used as an example. Successful bulk chemical cell factories in recent years were then summarized

including L-alanine

L-methionine

succinate

D-lactate

malonate

L-malate

glutarate

adipate

3-propanediol

4-butanediol

isobutanol

etc

. In the future

further increasing the efficiency of substrates utilization and broadening the range of products wi

ll be the directions of development of microbial cell factories

but the design and engineering of new enzymes are the key bottleneck limiting the design of metabolic pathways. It is believed that with the deepening of research

microbial cell factories will be more widely used in the production of bulk chemicals besides chemical methods.

关键词

Keywords

references

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