工程微生物合成苯丙酸类化合物及其衍生物的研究进展

doi:10.12211/2096-8280.2020-014

合成生物学 ›› 2020, Vol. 1 ›› Issue (3): 337-357.DOI: 10.12211/2096-8280.2020-014

工程微生物合成苯丙酸类化合物及其衍生物的研究进展

牛福星¹, 杜云平², 黄远斌¹, 周荷田², 刘建忠¹

^1.中山大学生命科学学院合成生物学研究所，生物无机与合成化学教育部重点实验室，广东省水生经济动物良种繁育重点实验室，广东广州 510275
^2.温氏食品集团股份有限公司，广东云浮 527400

收稿日期:2020-03-02 修回日期:2020-04-14 出版日期:2020-06-30 发布日期:2020-09-29
通讯作者: 刘建忠
作者简介:牛福星（1988—），男，博士，博士后。研究方向为微生物代谢工程与合成生物学。E-mail: niufx3@mail.sysu.edu.cn|刘建忠（1966—），男，博士，教授。研究方向为微生物代谢工程与合成生物学。E-mail: lssljz@mail.sysu.edu.cn
基金资助:
国家自然科学基金(21808248);广东省基础与应用基础研究基金(2019B1515210006);深圳合成生物学创新研究院对外开放基金(DWKF20190003)

Recent advances in the production of phenylpropanoic acids and their derivatives by genetically engineered microorganisms

Fuxing NIU¹, Yunping DU², Yuanbin HUANG¹, Hetian ZHOU², Jianzhong LIU¹

^1.Institute of Synthetic Biology，MOE Key Laboratory of Bioinorganic and Synthetic Chemistry，Guangdong Province Key Laboratory of Improved Variety Reproduction in Aquatic Economic Animals，School of Life Sciences，Sun Yat-Sen University，Guangzhou 510275，Guangdong，China
^2.Wens Foodstuff Group CO. ，Ltd. ，Yunfu 527400，Guangdong，China

Received:2020-03-02 Revised:2020-04-14 Online:2020-06-30 Published:2020-09-29
Contact: Jianzhong LIU

摘要/Abstract

摘要：

苯丙酸类化合物是一类重要的苯丙素类化合物，是指含C₆-C₃单元的天然有机酸，包括苯丙烯酸类和苯乳酸类化合物。许多苯丙酸类化合物具有抗氧化、抑菌、增强免疫力、抗癌、抗病毒、抗炎、降血脂、治疗心血管疾病等生物学活性，广泛应用于食品、医药、香料、化妆品、农业等领域。苯丙酸类化合物是经由莽草酸合成途径合成的苯丙氨酸或酪氨酸衍生物。随着代谢工程和合成生物学的发展，成功构建了一些微生物以合成苯丙酸类化合物及其衍生物。为此，本文系统综述了工程微生物合成苯丙酸类化合物及其衍生物的进展，包括肉桂酸、苯乙烯、对香豆酸、对羟基苯乙烯、对香豆酸-莽草酸、咖啡酸、绿原酸、3，4-二羟基苯乙烯、阿魏酸、姜黄素、左旋多巴、苯乳酸、对羟基苯乳酸、丹参素和迷迭香酸。其后，归纳了应用于微生物合成芳香化合物的主要合成生物学策略。最后，对合成苯丙酸类化合物及其衍生物的工程微生物的发展趋势进行了展望。本文旨在为合成苯丙酸类化合物及其衍生物的人工微生物的创制提供指导。

关键词: 工程微生物, 苯丙酸类化合物及其衍生物, 代谢工程, 合成生物学, 生物合成, 菌种构建

Abstract:

Phenylpropanoic acids are important phenylpropanoid compounds, which are natural organic acids containing the C₆-C₃ unit, including phenylacrylic acid and phenyllactic acid compounds. Many phenylpropanoic acids have activities in antioxidation, antibacteria, antitumors, antivirus, anti-inflammation, immunity enhancement, reducing blood lipids, and treating cardiovascular diseases. Phenylpropanoic acids are widely used in food, medicine, flavor, cosmetics, agriculture, and so forth. In plants, phenylpropanoids are synthesized from L-phenylalanine or L-tyrosine derived from the shikimate pathway. To overcome the drawbacks of their extract from plants, biotechnological production is a good alternative. With advances in metabolic engineering and synthetic biology, many microorganisms have been engineered to produce phenylpropanoic acids and their derivatives. Herein, we systematically and comprehensively review recent advancements in the production of phenylpropanoic acids and their derivatives by metabolic engineered microorganisms. These compounds include cinnamic acid, styrene, p-coumaric acid, p-hydroxystyrene, p-coumaroyl shikimate, caffeic acid, chlorogenic acid, 3,4-hydroxystyrene, ferulic acid, curcumin, L-DOPA, phenyllactic acid, p-hydroxyphenyllactic acid, salvianic acid A, and rosmarinic acid. Then, some main synthetic biology strategies for the microbial production of the aromatics are summarized. Finally, future perspectives about engineering microorganisms for producing phenylpropanoids are discussed. Some strategies are proposed: 1) tolerance engineering using biosensor-based adaptive laboratory evolution; 2) oxidative engineering; 3) modular coculture engineering; 4) systems metabolic engineering.

Key words: engineered microorganisms, phenylpropanoic acids and their derivatives, metabolic engineering, synthetic biology, biosynthesis, strain construction

中图分类号:

Q 78

牛福星, 杜云平, 黄远斌, 周荷田, 刘建忠. 工程微生物合成苯丙酸类化合物及其衍生物的研究进展[J]. 合成生物学, 2020, 1(3): 337-357.

Fuxing NIU, Yunping DU, Yuanbin HUANG, Hetian ZHOU, Jianzhong LIU. Recent advances in the production of phenylpropanoic acids and their derivatives by genetically engineered microorganisms[J]. Synthetic Biology Journal, 2020, 1(3): 337-357.

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工程微生物合成苯丙酸类化合物及其衍生物的研究进展

Recent advances in the production of phenylpropanoic acids and their derivatives by genetically engineered microorganisms

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