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http://dx.doi.org/10.4014/jmb.2008.08005

Fermentation and Metabolic Pathway Optimization to De Novo Synthesize (2S)-Naringenin in Escherichia coli  

Zhou, Shenghu (National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University)
Hao, Tingting (National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University)
Zhou, Jingwen (National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University)
Publication Information
Journal of Microbiology and Biotechnology / v.30, no.10, 2020 , pp. 1574-1582 More about this Journal
Abstract
Flavonoids have diverse biological functions in human health. All flavonoids contain a common 2-phenyl chromone structure (C6-C3-C6) as a scaffold. Hence, in using such a scaffold, plenty of high-value-added flavonoids can be synthesized by chemical or biological catalyzation approaches. (2S)-Naringenin is one of the most commonly used flavonoid scaffolds. However, biosynthesizing (2S)-naringenin has been restricted not only by low production but also by the expensive precursors and inducers that are used. Herein, we established an induction-free system to de novo biosynthesize (2S)-naringenin in Escherichia coli. The tyrosine synthesis pathway was enhanced by overexpressing feedback inhibition-resistant genes (aroGfbr and tyrAfbr) and knocking out a repressor gene (tyrR). After optimizing the fermentation medium and conditions, we found that glycerol, glucose, fatty acids, potassium acetate, temperature, and initial pH are important for producing (2S)-naringenin. Using the optimum fermentation medium and conditions, our best strain, Nar-17LM1, could produce 588 mg/l (2S)-naringenin from glucose in a 5-L bioreactor, the highest titer reported to date in E. coli.
Keywords
L-tyrosine; p-coumaric acid; dynamic regulation; flavonoids; temperature-shift;
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