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

• Published in: Journal of agricultural and food chemistry 2020-01, Vol.68 (4), p.1015-1021
• Main Authors: Gao, Song, Lyu, Yunbin, Zeng, Weizhu, Du, Guocheng, Zhou, Jingwen, Chen, Jian
• Format: Article
• Language: English
• Subjects: Biosynthetic Pathways; Coumaric Acids - metabolism; Flavanones - biosynthesis; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/acs.jafc.9b05218

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