Engineered synthesis of rosmarinic acid in Escherichia coli resulting production of a new intermediate, caffeoyl-phenyllactate.

Abstract

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. 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. 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.