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
[ "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" ]
收稿:2020-03-02,
修回:2020-04-14,
纸质出版:2020-06-30
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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
NIU Fuxing, DU Yunping, HUANG Yuanbin, ZHOU Hetian, LIU Jianzhong. Recent advances in the production of phenylpropanoic acids and their derivatives by genetically engineered microorganisms[J]. Synthetic Biology Journal, 2020, 1(3): 337-357
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 DOI: 10.12211/2096-8280.2020-014.
NIU Fuxing, DU Yunping, HUANG Yuanbin, ZHOU Hetian, LIU Jianzhong. Recent advances in the production of phenylpropanoic acids and their derivatives by genetically engineered microorganisms[J]. Synthetic Biology Journal, 2020, 1(3): 337-357 DOI: 10.12211/2096-8280.2020-014.
苯丙酸类化合物是一类重要的苯丙素类化合物,是指含C
6
-C
3
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。
Phenylpropanoic acids are important phenylpropanoid compounds
which are natural organic acids containing the C
6
-C
3
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 phenylpr
opanoic 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.
2
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