Journal
SYNTHETIC BIOLOGY
Volume 5, Issue 1, Pages -Publisher
OXFORD UNIV PRESS
DOI: 10.1093/synbio/ysaa012
Keywords
pathway engineering; flavonoids; synthetic biology; metabolic engineering; flavanones
Funding
- Biotechnology and Biological Sciences Research Council (BBSRC)
- Engineering and Physical Sciences Research Council (EPSRC) under grant: 'Centre for synthetic biology of fine and specialty chemicals (SYNBIOCHEM)' [BB/M017702/1]
- European Union [814408]
- French National Funding Agency [ANR-15-CE1-0008]
- Engineering and Physical Sciences Research Council (EPSRC) under grant: 'Future Biomanufacturing Research Hub' [EP/S01778X/1]
- BBSRC [BB/M017702/1] Funding Source: UKRI
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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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