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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2020, Vol. 40 Issue (7): 91-99    DOI: 10.13523/j.cb.2002025
综述     
微生物异源合成咖啡酸及其酯类衍生物研究进展 *
王震,李霞(),元英进
天津大学化工学院 教育部合成生物学前沿科学中心 系统生物工程教育部重点实验室 天津 300072
Advances in Production of Caffeic Acid and Its Ester Derivatives in Heterologous Microbes
WANG Zhen,LI Xia(),YUAN Ying-jin
Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering, Ministry of Education, Tianjin University, Tianjin 300072, China
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摘要：

咖啡酸及其酯类衍生物如绿原酸、迷迭香酸和咖啡酸苯乙酯等具有天然抗氧化、抗肿瘤、抗病毒和抗炎等重要的药理活性,具有广阔的药用开发前景。从天然药物中提取或者化学合成咖啡酸及其酯类衍生物,存在含量低、提取效率不高、催化成本高昂以及环境污染等问题。随着咖啡酸及其酯类衍生物合成途径解析和合成生物学的快速发展,微生物异源合成咖啡酸及其酯类衍生物的研究已逐渐展开。对微生物异源合成咖啡酸及其酯类衍生物合成途径的最新进展以及代谢工程策略进行了综述,并讨论了目前存在的问题和未来的发展趋势。
关键词： 咖啡酸;  咖啡酸酯类衍生物;  合成生物学    
Abstract:

Caffeic acid and its ester derivatives like chlorogenic acid, rosmarinic acid, and caffeic acid phenethyl ester have important pharmacological activities such as natural antioxidant, antitumor, antiviral, and anti-inflammatory, and have broad prospects for medical development. Traditional extraction and chemical synthesis of caffeic acid and its derivatives from plants exist some problems such as low content, low extraction efficiency, high catalytic cost, and environmental pollution. In recent years, the study of heterologous synthesis of caffeic acid and its ester derivatives by microbes has been gradually carried out with the rapid development of synthetic biology.The recent advances in the biosynthetic pathway elucidations of caffeic acid and its ester derivatives and metabolic engineering strategies in heterologous microbes were summarized, and the current status as well as future perspectives were discussed.
Key words: Caffeic acid    Caffeic acid ester derivatives    Synthetic biology
收稿日期: 2020-02-18 出版日期: 2020-08-13
ZTFLH:  Q815  
基金资助: * 国家自然科学基金资助项目(81502976)
通讯作者: 李霞     E-mail: lixia01@tju.edu.cn
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王震,李霞,元英进. 微生物异源合成咖啡酸及其酯类衍生物研究进展 *[J]. 中国生物工程杂志, 2020, 40(7): 91-99.

WANG Zhen,LI Xia,YUAN Ying-jin. Advances in Production of Caffeic Acid and Its Ester Derivatives in Heterologous Microbes. China Biotechnology, 2020, 40(7): 91-99.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2002025    或    https://manu60.magtech.com.cn/biotech/CN/Y2020/V40/I7/91

图1  咖啡酸及其常见酯类衍生物化学结构
图2  异源生物合成路径
Product Precursor Carbon source Heterologous
enzymes		 Source Titer Host Ref.
Caffeic acid p-coumaric acid Glycerol CYP199A2
pdR
pux		 R. palustris
P. putida
R. palustris		 2.8g/L E.coli [17]
p-coumaric acid Glycerol hpaBC P.aeruginosa PAO1 10.2g/L E.coli [19]
Tyrosine Glucose TAL
hpaB
hpaC		 R. toruloides
P. aeruginosa
S. enterica		 289mg/L S. cerevisiae [20]
No added Glucose+
Glycerol		 TAL
hpaBC		 R. capsulatus
E. coli MG1655		 50.2mg/L E.coli [5]
No added Cellulose from
Kraft pulp		 fevV
hpaBC		 Streptomyces sp.
WK-5344
P.aeruginosa PAO1		 233mg/L E.coli [16]
Rosmarinic acid No added Glucose HdhA
hpaBC
TAL
4CL
RAS		 L. delbrueckii
E. coli
R. sphaeroides
A. thaliana
M. officinalis		 1.8μmol/L E.coli [7]
Caffeic acid Glucose LDH
hpaBC
4CL
RAS		 L. pentosus
E. coli
A.thaliana
Coleus blumei		 130mg/L E.coli [8]
Chlorogenic acid Caffeic acid Glucose 4CL
HQT
ydiB		 O. sativa
N. tobacco
E. coli		 450mg/L E.coli [10]
No added Glucose TAL
hpaBC
4CL
HQT
ydiB		 S.espanaensis
E. coli
O. sativa
N. tobacco
E. coli		 78mg/L E.coli [11]
Caffeic acid
phenethyl esters		 No added Glucose TAL
hpaBC
4CL
KDC
ADH
O-ATF		 R. glutinis
E. coli
A. thaliana
Lactococcus lactis
S. cerevisiae
S. cerevisiae		 60mg/L E.coli [13]
表1  微生物异源合成咖啡酸及其酯类衍生物
图3  莽草酸途径代谢调控
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