Engineering Escherichia coli towards de novo production of gatekeeper (2S)-flavanones: naringenin, pinocembrin, eriodictyol and homoeriodictyol.

Synthetic Biology
Mark S DunstanNigel S Scrutton

Abstract

Natural plant-based flavonoids have drawn significant attention as dietary supplements due to their potential health benefits, including anti-cancer, anti-oxidant and anti-asthmatic activities. Naringenin, pinocembrin, eriodictyol and homoeriodictyol are classified as (2S)-flavanones, an important sub-group of naturally occurring flavonoids, with wide-reaching applications in human health and nutrition. These four compounds occupy a central position as branch point intermediates towards a broad spectrum of naturally occurring flavonoids. Here, we report the development of Escherichia coli production chassis for each of these key gatekeeper flavonoids. Selection of key enzymes, genetic construct design and the optimization of process conditions resulted in the highest reported titers for naringenin (484 mg/l), improved production of pinocembrin (198 mg/l) and eriodictyol (55 mg/l from caffeic acid), and provided the first example of in vivo production of homoeriodictyol directly from glycerol (17 mg/l). This work provides a springboard for future production of diverse downstream natural and non-natural flavonoid targets.

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Citations

Dec 22, 2020·Synthetic Biology·Pablo CarbonellNigel S Scrutton
Jan 8, 2021·Frontiers in Bioengineering and Biotechnology·Ahmad Bazli RamziNigel S Scrutton
May 7, 2021·Essays in Biochemistry·Dongsoo YangSang Yup Lee
Jun 9, 2021·Biochemical Society Transactions·Christopher J RobinsonNigel S Scrutton
Jun 3, 2021·Microorganisms·Alec BannerNigel S Scrutton
Aug 8, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hanghang LouQihe Chen

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Methods Mentioned

BETA
gene double knockout

Software Mentioned

Selenzyme
Excel
MassLynx

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