化学品体外生物合成途径设计、元件组装和应用

doi:10.12211/2096-8280.2021-019

合成生物学 ›› 2021, Vol. 2 ›› Issue (6): 886-901.DOI: 10.12211/2096-8280.2021-019

化学品体外生物合成途径设计、元件组装和应用

万逸尘^1,², 许孔亮^1,², 郑仁朝^1,², 郑裕国^1,²

^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

收稿日期:2021-02-06 修回日期:2021-04-30 出版日期:2021-12-31 发布日期:2022-01-21
通讯作者: 郑仁朝
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
基金资助:
国家重点研发计划(2017YFE0129400);浙江省自然科学基金(LR19B060001)

In vitro biosynthesis of chemicals: pathway design, component assembly and applications-a review

Yichen WAN^1,², Kongliang XU^1,², Renchao ZHENG^1,², Yuguo ZHENG^1,²

^1.Key Laboratory of Bioorganic Synthesis of Zhejiang Province，College of Biotechnology and Bioengineering，Zhejiang University of Technology，Hangzhou 310014，Zhejiang，China
^2.Engineering Research Center of Bioconversion and Biopurification of Ministry of Education，Zhejiang University of Technology，Hangzhou 310014，Zhejiang，China

Received:2021-02-06 Revised:2021-04-30 Online:2021-12-31 Published:2022-01-21
Contact: Renchao ZHENG

摘要/Abstract

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。

关键词: 体外生物合成, 化学品制造, 途径设计, 蛋白质工程, 酶元件

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 viain vitro biosynthesis have also been summarized, including glucosamine, glycerol glucoside, pyruvate, α-ketoglutarate, ethanol, 1,3-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 biosynthesis 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.

Key words: in vitro biosynthesis, chemicals production, pathway design, protein engineering, enzyme component

中图分类号:

Q591.1

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.

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

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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

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