化学品体外生物合成途径设计、元件组装和应用

万逸尘; 许孔亮; 郑仁朝; 郑裕国

doi:10.12211/2096-8280.2021-019

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化学品体外生物合成途径设计、元件组装和应用

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- 化学品体外生物合成途径设计、元件组装和应用
- In vitro biosynthesis of chemicals: pathway design, component assembly and applications-a review
- 合成生物学 2021年2卷第6期页码：886-901
- 作者机构：
  
  1.浙江工业大学生物工程学院，生物有机合成技术研究浙江省重点实验室，浙江杭州 310014
  2.浙江工业大学生物工程学院，生物转化与生物净化教育部工程研究中心，浙江杭州 310014
- 作者简介：
  
  [ "万逸尘（1996—），男，博士研究生。研究方向为无细胞酶催化与多酶蛋白结构组装等。E-mail：459377623@qq.com" ]
  [ "郑仁朝（1980—），男，博士，教授。研究方向为工业生物催化应用基础和产业化研究等。E-mail：zhengrc@zjut.edu.cn" ]
- 基金信息：
  
  国家重点研发计划(2017YFE0129400);浙江省自然科学基金(LR19B060001;LQ20E020009)
- DOI：10.12211/2096-8280.2021-019
  中图分类号： Q591.1
- 收稿：2021-02-06，
  
  修回：2021-04-30，
  
  纸质出版：2021-12-31
- 稿件说明：
移动端阅览
万逸尘，许孔亮，郑仁朝，郑裕国. 化学品体外生物合成途径设计、元件组装和应用［J］. 合成生物学， 2021， 2（6）： 886-901

WAN Yichen， XU Kongliang， ZHENG Renchao， ZHENG Yuguo. In vitro biosynthesis of chemicals： pathway design， component assembly and applications - a review［J］. Synthetic Biology Journal， 2021， 2（6）： 886-901
万逸尘，许孔亮，郑仁朝，郑裕国. 化学品体外生物合成途径设计、元件组装和应用［J］. 合成生物学， 2021， 2（6）： 886-901 DOI： 10.12211/2096-8280.2021-019.

WAN Yichen， XU Kongliang， ZHENG Renchao， ZHENG Yuguo. In vitro biosynthesis of chemicals： pathway design， component assembly and applications - a review［J］. Synthetic Biology Journal， 2021， 2（6）： 886-901 DOI： 10.12211/2096-8280.2021-019.

摘要

随着合成生物技术的发展，体外生物合成逐渐成为化学品合成的重要方式之一，具有环境友好、催化效率高、原子经济性好、可控性强等优点。途径设计是构建整个体外生物合成系统的关键所在，本文分析总结了体外生物合成中应遵循的两个重要原则，包括原子经济性原则和能量最优原则。利用生物大分子将酶元件组装构建成多酶复合体，可提高体外生物合成的反应速率、减少副反应的发生，本文介绍了用于酶元件组装的3类常见生物大分子，包括连接肽、蛋白支架、DNA等。通过近年来体外生物合成在大宗化学品（糖类化学品、有机酸类化学品以及醇类化学品等）生产中的应用案例的介绍，展示了体外生物合成在化学品合成中的应用前景。随着体外生物合成设计能力的不断提高，体外生物合成的途径设计将朝着智能化、高效化发展，化学品体外生物合成的效率也将逐步提高，有望涵盖所有化学品的生物合成，成为未来化学品合成的主要方式之一。

Abstract

Chemical industry is one of the pillar industries in the modern society. The demand for refined chemicals with high-quality and diversity is rapidly increasing with the improvement of society and human being's living standards. As a supplement to conventional chemical synthesis

environmental friendly biosynthesis is attracting widespread attention and will be an important step to achieve a sustainable development.

In vitro

biosynthesis (cell free biosynthesis) is a synthetic method to prepare desired chemicals

which was catalyzed by purified enzymes or cell extracts. With the development of synthetic biotechnology

in vitro

biosynthesis has gradually become one of the most important ways for chemicals production

exhibiting the advantages of environmental friendliness

high catalytic efficiency

good atom economy and strong controllability. Pathway design is the key for the construction of

in vitro

biosynthesis system. In this review

two important principles for designing

in vitro

biosynthetic pathways have been summarized

including atom economy and energy optimization. As one of the important concepts of green chemistry

principle atom economy means that the synthesis method or process should be designed to convert raw materials into the final product as much as possible. Principle energy optimization means that the ATP-free or ATP minimized process should be designed in the synthesis method. Assembly enzymes into a multi-enzyme complex

via

biological macromolecules can increase reaction rate and also reduce the side reactions of the

in vitro

biosynthesis. Thus

three common-used biological macromolecules for enzyme assembly will be introduced here

including peptide linkers

protein scaffolds

DNA. Some recent examples of chemicals produced

via

in vitro

biosynthesis have also been summarized

including glucosamine

glycerol glucoside

pyruvate

-ketoglutarate

ethanol

3-propanediol

islatravir

azomycin

and

etc

. Through the introduction of

in vitro

biosynthesis of bulk chemicals (carbohydrate chemicals

organic acid chemicals

alcohol chemicals

and etc.)

this article demonstrates the potentials of

in vitro

biosynthesis in chemical synthesis. By reviewing the pathway design

enzyme component assembly and chemicals production examples

the future of

in vitro

biosynthesis of chemicals has been prospected here. With the design improvement of

in vitro

biosynthesis

the pathway designing will be becoming more and more intelligent and efficient. It is believed that the efficiency of

in vitro

biosynth

esis of chemicals will be gradually increased and the

in vitro

biosynthesis hopefully can cover all chemicals' production

which is expected to be one of the predominant ways for chemicals production in the future.

关键词

Keywords

references

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