Combinatorial mutasynthesis of flavonoid analogues from acrylic acids in microorganisms.

Flavonoids are plant secondary metabolites often used as nutraceutical supplements, but a growing number of unnatural flavonoids are being investigated as therapeutic agents. Cultures of Saccharomyces cerevisiae expressing recombinant flavonoid enzymes, including 4-coumaroyl:CoA ligase (4CL), chalcone synthase (CHS), chalcone isomerase (CHI), and flavanone 3beta-hydroxylase (FHT), produced novel flavanones and dihydroflavonols when fed with a number of aromatic acrylic acids. The flavonoid network also exhibited broad substrate specificity by converting muconic acid into a unique polypropanoid.