Background: l-2-aminobutyric acid (l-ABA) is an unnatural amino acid that is a key intermediate for the synthesis of several important pharmaceuticals. To make the biosynthesis of l-ABA environmental friendly and more suitable for the industrial-scale production. We expand the nature metabolic network of Escherichia coli using metabolic engineering approach for the production of l-ABA. Results: In this study, Escherichia coli THR strain with a modified pathway for threonine-hyperproduction was engineered via deletion of the rhtA gene from the chromosome. To redirect carbon flux from 2-ketobutyrate (2-KB) to l-ABA, the ilvIH gene was deleted to block the l-isoleucine pathway. Furthermore, the ilvA gene from Escherichia coli W3110 and the leuDH gene from Thermoactinomyces intermedius were amplified and co-overexpressed. The promoter was altered to regulate the expression strength of ilvA∗and leuDH. The final engineered strain E. coli THR ΔrhtAΔilvIH/Gap-ilvA∗-Pbs-leuDH was able to produce 9.33 g/L of l-ABA with a yield of 0.19 g/L/h by fed-batch fermentation in a 5 L bioreactor. Conclusions: This novel metabolically tailored strain offers a promising approach to fulfill industrial requirements for production of l-ABA.
CITATION STYLE
Xu, J. M., Li, J. Q., Zhang, B., Liu, Z. Q., & Zheng, Y. G. (2019). Fermentative production of the unnatural amino acid l-2-aminobutyric acid based on metabolic engineering. Microbial Cell Factories, 18(1). https://doi.org/10.1186/s12934-019-1095-z
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