Engineering of the aromatic amino acid biosynthetic pathways in Escherichia coli for the production of value-added chemicals
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Aromatic amino acids (AAAs) L-phenylalanine, L-tyrosine and L-tryptophan serve not only as the building blocks for protein synthesis, but also as the precursors of secondary metabolites in organisms. A number of AAA-derived metabolites have shown pharmaceutical or industrial importance. However, these molecules usually occur in nature at low abundance, which greatly limits their efficient isolation, production and broad applications. In past decades, the development of metabolic engineering and synthetic biology facilitated the construction of ‘microbial chemical factories’ that convert renewable carbon sources to various valuable molecules. This dissertation focuses on the engineering of the E. coli AAA biosynthetic pathways to achieve the heterologous production of pharmaceutically and industrially important chemicals derived from AAAs or its biosynthetic intermediates. After careful evaluation, we select several important target compounds, including caffeic acid, simple coumarins, salicylic acid, muconic acid and 5-hydroxytryptophan and explore their production in E. coli. For this purpose, we designed, reconstituted and optimized their respective artificial biosynthetic pathways, and also conducted the modification of the E. coli native shikimate pathway via combinatorial metabolic engineering approaches. This research established powerful microbial platforms for the production of AAA related value-added chemicals, exhibiting great potential for commercialized production.