Glycosylation Modification Enhances (2 S )-Naringenin Production in Saccharomyces cerevisiae .

(2 S )-Naringenin is an important flavonoid precursor, with multiple nutritional and pharmacological activities. Both (2 S )-naringenin and other flavonoid production are hindered by poor water solubility and inhibited cell growth. To address this, we increased solubility and improved cell growth by partially glycosylating (2 S )-naringenin to naringenin-7-O-glucoside, which facilitated increased extracellular secretion, by knocking out endogenous glycosyl hydrolase genes, EXG1 and SPR1 , and expressing the glycosyltransferase gene ( UGT733C6 ). Naringenin-7-O-glucoside synthesis was further improved by optimizing UDP-glucose and shikimate pathways. Then, hydrochloric acid was used to hydrolyze naringenin-7-O-glucoside to (2 S )-naringenin outside the cell. Thus, our optimized Saccharomyces cerevisiae strain E32T19 produced 1184.1 mg/L (2 S )-naringenin, a 7.9-fold increase on the starting strain. Therefore. we propose that glycosylation modification is a useful strategy for the efficient heterologous biosynthesis of (2 S )-naringenin in S. cerevisiae .