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Abstract
Microbial-based chemical production from renewable and cheap carbon sources serves as a green replacement to petroleum-based chemical production or plant-based extraction of natural products. The enabling technology, known as metabolic engineering, incorporates enzyme mining, synthetic pathway design and assembly, and systematic host engineering to improve titers, productivities and yields of target products in microbial hosts. To expand the chemical space accessible from microbial-based system, a key principle of metabolic engineering design is to extend existing metabolic pathways and redirect carbon flux en route to these native metabolic pathways. This takes advantage of native metabolic highways and reduce toxic or foreign intermediates or bottleneck enzymes that may impair cell fitness or production performance. Herein, we focused on extending amino acid pathways in Escherichia coli and designing synthetic pathways to produce new chemical products. By extending aromatic amino acid pathways, we were able to produce high-value natural products including caffeic acid derived phenethyl esters and amides, and improve the production of tryptophan and its pathway derivatives anthranilate and muconic acid. Then, by extending charged amino acid pathways, we established a novel metabolic platform capable of producing industrially important C3-C5 diols from amino acids. With the presented platform, seven different diol-convertible amino acids can be converted to diols including 1,3 propanediol (1,3 PDO), 1,4-butanediol (1,4 BDO) and 1,5-pentanediol (1,5 PDO). Finally, by harnessing acetyl-CoA mediated carbon extension pathways, two C5 dicarboxylates, glutarate and 2-methyl-succinate, were successfully produced with applications as bioplastic monomers. Our work presents new metabolic platforms that enriches the pathway repertoire for both natural and non-natural chemical products by extending existing microbial metabolic infrastructures.