Synthesis of unnatural flavonoids and stilbenes by exploiting the plant biosynthetic pathway in Escherichia coli.
Flavonoids and stilbenes have attracted much attention as potential targets for nutraceuticals, cosmetics, and pharmaceuticals. We have developed a system for producing "unnatural" flavonoids and stilbenes in Escherichia coli. The artificial biosynthetic pathway included three steps. These included a substrate synthesis step for CoA esters synthesis from carboxylic acids by 4-coumarate:CoA ligase, a polyketide synthesis step for conversion of the CoA esters into flavanones by chalcone synthase and chalcone isomerase, and into stilbenes by stilbene synthase, and a modification step for modification of the flavanones by flavone synthase, flavanone 3beta-hydroxylase and flavonol synthase. Incubation of the recombinant E. coli with exogenously supplied carboxylic acids led to production of 87 polyketides, including 36 unnatural flavonoids and stilbenes. This system is promising for construction of a larger library by employing other polyketide synthases and modification enzymes.
Katsuyama
Yohei
Y
Department of Biotechnology, Graduate School of Agriculture and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
Funa
Nobutaka
N
Miyahisa
Ikuo
I
Horinouchi
Sueharu
S
D002264:Carboxylic Acids / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D005419:Flavonoids / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D017343:Genes, Plant / Q000502:physiology; D015394:Molecular Structure; D010944:Plants / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D010957:Plasmids; D048630:Polyketide Synthases / Q000235:genetics / Q000378:metabolism; D013267:Stilbenes / Q000737:chemistry; D013379:Substrate Specificity
D002264:Carboxylic Acids; D005419:Flavonoids; D013267:Stilbenes; D048630:Polyketide Synthases