Engineered synthesis of rosmarinic acid in Escherichia coli resulting production of a new intermediate, caffeoyl-phenyllactate.
OBJECTIVE
To achieve high production of rosmarinic acid and derivatives in Escherichia coli which are important phenolic acids found in plants, and display diverse biological activities.


RESULTS
The synthesis of rosmarinic acid was achieved by feeding caffeic acid and constructing an artificial pathway for 3,4-dihydroxyphenyllactic acid. Genes encoding the following enzymes: rosmarinic acid synthase from Coleus blumei, 4-coumarate: CoA ligase from Arabidopsis thaliana, 4-hydroxyphenyllactate 3-hydroxylase from E. coli and D-lactate dehydrogenase from Lactobacillus pentosus, were overexpressed in an L-tyrosine over-producing E. coli strain. The yield of rosmarinic acid reached ~130 mg l(-1) in the recombinant strain. In addition, a new intermediate, caffeoyl-phenyllactate (~55 mg l(-1)), was also produced by the engineered E. coli strain.


CONCLUSIONS
This work not only leads to high yield production of rosmarinic acid and analogues, but also sheds new light on the construction of the pathway of rosmarinic acid in E. coli.
Department of Food Science and Technology, School of Biological Engineering, East China University of Science and Technology, Shanghai, 200237, China.|Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.
Jingjie
J
Jiang
Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.|Key Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.
Huiping
H
Bi
Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.|Key Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.
Yibin
Y
Zhuang
Department of Food Science and Technology, School of Biological Engineering, East China University of Science and Technology, Shanghai, 200237, China. swliu@ecust.edu.cn.
Shaowei
S
Liu
Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China. liu_t@tib.cas.cn.|Key Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China. liu_t@tib.cas.cn.
Tao
T
Liu
Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.
Yanhe
Y
Ma
D002109:Caffeic Acids / Q000737:chemistry; D002934:Cinnamates / Q000378:metabolism*; D053630:Depsides / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D060847:Metabolic Engineering / Q000379:methods; D013379:Substrate Specificity; D000097123:Rosmarinic Acid
D002109:Caffeic Acids; D002934:Cinnamates; D053630:Depsides; D029968:Escherichia coli Proteins; D000097123:Rosmarinic Acid; C040048:caffeic acid
4-Coumarate CoA ligase; Biosynthesis; Caffeoyl-phenyllactate; Escherichia coli; Rosmarinic acid; Rosmarinic acid synthase