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

Abstract

However, the added tyrosine and p-coumaric acid increase the cost of fermentation. Hence, cheaper carbon sources are preferred in the fermentation process. To synthesize (2S)-naringenin from glucose, Wu et al. overexpressed 3-deoxy-D-arabinoheptulosonate-7-phosphate (DAHP) synthase (aroG fbr ) and chorismate mutase/prephenate dehydrogenase (tyrA fbr ) in E. coli. This released the feedback inhibition by tyrosine to finally yield 100.64 mg/l (2S)-naringenin Furthermore, Raman et al. obtained 61 mg/l of (2S)-naringenin from Flavonoids have diverse biological functions in human health. All flavonoids contain a common 2phenyl chromone structure (C6-C3-C6) as a scaffold. Hence, in using such a scaffold, plenty of highvalue-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 (aroG fbr and tyrA fbr ) 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.

Topics & Concepts