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

Dunstan, Mark S ; Robinson, Christopher J ; Jervis, Adrian J ; Yan, Cunyu ; Carbonell, Pablo ; Hollywood, Katherine A ; Currin, Andrew ; Swainston, Neil ; Feuvre, Rosalind Le ; Micklefield, Jason ; Faulon, Jean-Loup ; Breitling, Rainer ; Turner, Nicholas ; Takano, Eriko ; Scrutton, Nigel S

ACS synthetic biology, 2020-01, Vol.5 (1), p.ysaa012-ysaa012 [Periódico revisado por pares]

England: Oxford University Press

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  • Título:
    Engineering Escherichia coli towards de novo production of gatekeeper (2 S )-flavanones: naringenin, pinocembrin, eriodictyol and homoeriodictyol
  • Autor: Dunstan, Mark S ; Robinson, Christopher J ; Jervis, Adrian J ; Yan, Cunyu ; Carbonell, Pablo ; Hollywood, Katherine A ; Currin, Andrew ; Swainston, Neil ; Feuvre, Rosalind Le ; Micklefield, Jason ; Faulon, Jean-Loup ; Breitling, Rainer ; Turner, Nicholas ; Takano, Eriko ; Scrutton, Nigel S
  • Assuntos: Asthma ; Dietary supplements ; Enzymes ; Escherichia coli ; Glycerin ; Glycerol ; Isoflavones ; Life Sciences
  • É parte de: ACS synthetic biology, 2020-01, Vol.5 (1), p.ysaa012-ysaa012
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
    PMCID: PMC7644443
    Mark S Dunstan, Christopher J Robinson and Adrian J Jervis contributed equally to this work.
  • Descrição: 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 (2 )-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 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 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.
  • Editor: England: Oxford University Press
  • Idioma: Inglês

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