Enhancing caffeic acid production in Escherichia coli by engineering the biosynthesis pathway and transporter

Caffeic acid is a phenylpropanoid which is widely used in medical industry. Microbial fermentation provides a green strategy for producing caffeic acid. To improve the capacity for caffeic acid production in Escherichia coli, the competing pathways for l-tyrosine synthesis were knocked out. The biosynthesis pathway of the cofactor FAD and the expression of previously reported polyphenol transporters were enhanced to promote the production of caffeic acid. Transcriptomics analysis was conducted to mine potential transporters that could further enhance the titer of caffeic acid in engineered E. coli. Transcriptomics data of E. coli under caffeic acid and ferulic acid stress showed that 19 transporters were upregulated. Among them, overexpression of ycjP, which was previously identified as a sugar ABC transporter permease, improved the caffeic acid titer to 775.7 mg/L. The caffeic acid titer was further improved to 7922.0 mg/L in a 5-L fermenter, the highest titer achieved by microorganisms.