Efficient Biosynthesis of (2S)-Naringenin from p-Coumaric Acid in Saccharomyces cerevisiae

(2 S )-Naringenin, a (2 S )-flavanone, is widely used in the food, chemical, and pharmaceutical industries because of its diverse physiological activities. The production of (2 S )-naringenin in microorganisms provides an ideal source that reduces the cost of the flavonoid. To achieve efficient production of (2 S )-naringenin in Saccharomyces cerevisiae ( S. cerevisiae ), we constructed a biosynthetic pathway from p -coumaric acid, a cost-effective and more efficient precursor. The (2 S )-naringenin synthesis pathway genes were integrated into the yeast genome to obtain a (2 S )-naringenin production strain. After gene dosage experiments, the genes negatively regulating the shikimate pathway and inefficient chalcone synthase activity were verified as factors limiting (2 S )-naringenin biosynthesis. With fed-batch process optimization of the engineered strain, the titer of (2 S )-naringenin reached 648.63 mg/L from 2.5 g/L p -coumaric acid. Our results indicate that the constitutive production of (2 S )-naringenin from p -coumaric acid in S. cerevisiae is highly promising.