Caffeic acid production from glucose using metabolically engineered Escherichia coli

Caffeic acid (3,4-dihydroxycinnamic acid) is a precursor for high-valued compounds with anticancer, antiviral activities, and anti-inflammatory making it an important substance in the food additive, cosmetics, and phar-maceutical industries. Here, we developed an engineered Escherichia coli strain capable of directly producing high levels of caffeic acid from glucose. Tyrosine ammonia-lyase from Rhodotorula glutinis (RgTAL) and p-cou-maric acid 3-hydroxylase from Saccharothrix espanaensis (SeC3H) were expressed. Next, feedback-resistant chorismate mutase/prephenate dehydrogenase, was introduced to promote L-tyrosine synthesis. This engi-neered strain CA3 produced 1.58 g/L of caffeic acid from glucose without tyrosine supplemented to the medium. Furthermore, to reduce p-coumaric acid accumulation, 4-hydroxyphenylacetate 3-hydroxylase from Pseudomonas aeruginosa (PaHpaBC) was introduced. Finally, an engineered strain CA8 directly produced 6.17 g/L of caffeic acid from glucose using a jar fermenter. The E. coli developed in this study would be helpful as a chassis strain to produce value-added caffeic acid-derivatives.