Construction of a Chimeric Biosynthetic Pathway for the De Novo Biosynthesis of Rosmarinic Acid in Escherichia coli

被引:43
作者
Bloch, Sarah E. [1 ]
Schmidt-Dannert, Claudia [1 ]
机构
[1] Univ Minnesota, Dept Biochem Mol Biol & Biophys, St Paul, MN 55108 USA
基金
美国国家卫生研究院;
关键词
biosynthesis; hydroxycinnamic acid esters; metabolic engineering; natural products; rosmarinic acid; D-LACTATE DEHYDROGENASE; HYDROXYCINNAMOYL-COA; RAT MODEL; TYRAMINE N-(HYDROXYCINNAMOYL)TRANSFERASE; FUNCTIONAL-CHARACTERIZATION; MELANIN PRODUCTION; CELL-CULTURES; COLEUS-BLUMEI; EXPRESSION; CLONING;
D O I
10.1002/cbic.201402275
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hydroxycinnamic acid esters (HCEs) are widely-distributed phenylpropanoid-derived plant natural products. Rosmarinic acid (RA), the most well-known HCE, shows promise as a treatment for cancer and neurological disorders. In contrast to extraction from plant material or plant cell culture, microbial production of HCEs could be a sustainable, controlled means of production. Through the overexpression of a six-enzyme chimeric bacterial and plant pathway, we show the de novo biosynthesis of RA, and the related HCE isorinic acid (IA), in Escherichia coli. Probing the pathway through precursor supplementation showed several potential pathway bottlenecks. We demonstrated HCE biosynthesis using three plant rosmarinic acid synthase (RAS) orthologues, which exhibited different levels of HCE biosynthesis but produced the same ratio of IA to RA. This work serves as a proof-of-concept for a microbial production platform for HCEs by using a modular biosynthetic approach to access diverse natural and non-natural HCEs.
引用
收藏
页码:2393 / 2401
页数:9
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