P155: Improvement of phenylpropanoic acids production via artificial biosynthetic pathway in tyrosine overproducing Escherichia coli

Phenylpropanoic acids, such as 4-coumaric acid, caffeic acid and ferulic acid, are the precursors to a range of important plant phenylpropanoids such as the secondary metabolites belonging to the flavonoid/stilbenoid class of compounds. Phenylpropanoic acids have attracted increasing attention for their various pharmaceutical properties as well as a valuable monomer for the production of liquid crystal polymers, which can be used for electronic applications. Although these compounds are widely used in human health care and industrial material, at present they are mainly obtained by extraction from plants and extraction yields are low because most of these metabolites accumulate at low levels in plant cells. We develop an Escherichia coli fermentation system that yields phenylpropanoic acids, such as 4-coumaric acid, caffeic acid, and ferulic acid, from simple carbon sources, using selected enzymes to construct an artificial biosynthetic pathway. This heterologous pathway extended E. coli native tyrosine biosynthesis machinery and was able to produce 4-coumaric acid, caffeic acid, and ferulic acid in minimal salt medium, respectively. Further improvement in production was accomplished by overproducing tyrosine biosynthesis in E. coli, which involved the alleviation of tyrosine-induced feedback inhibition. Finally, we achieved one gram per liter scale production of 4-coumaric acid. In addition, maximum titers of 150 mg/L of caffeic acid and 196 mg/L of ferulic acid were achieved in shake flasks after 36-hour cultivation. (Supported by grants from Basic Science Research program and Global Frontier Project (NRF) and Next-Generation BioGreen 21 Program (RDA, Republic of Korea))