Overproduction of hydroxytyrosol in Saccharomyces cerevisiae by heterologous overexpression of the Escherichia coli 4-hydroxyphenylacetate 3-monooxygenase

Hydroxytyrosol (HT), which is a polyphenol with a high antioxidant power and many associated health benefits, has been found in wines. Wine yeasts are capable of producing high amounts of the higher alcohol tyrosol, which is the precursor for HT synthesis. We have improved the ability of Saccharomyces cerevisiae to produce HT by heterologously expressing the HpaBC enzyme complex of Escherichia coli, which hydroxylates tyrosol into HT. By overexpressing the hpaB and hpaC genes, we achieved HT titers of 1.15 ± 0.05 mg/L and 4.6 ± 0.9 mg/L in a minimal medium in which either 1 mM tyrosine or 1 mM tyrosol were respectively added. This work demonstrates that the overexpression of HpaBC in yeast is a promising tool to overproduce HT at the expense of endogenous tyrosol through central carbon catabolism flux redirection to tyrosine catabolism.