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

Abstract

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