Improving (2S)-naringenin production by exploring native precursor pathways and screening higher-active chalcone synthases from plants rich in flavonoids

Flavonoids are a group of valuable compounds with a variety of health benefits. (2 S)-Naringenin is an important flavonoid skeleton, which can be tailored into almost all flavonoids. In this study, the Saccharomyces cerevisiae native precursor pathways were explored and higher-active CHSs from plants rich in flavonoids were screened. The results indicated that overexpressing the native precursor pathways is not an efficient approach to improving (2 S)-naringenin production in our chassis strain. On the other hand, by screening from plants rich in flavonoids, we obtained four CHSs with higher activities than the commonly used PhCHS. Among these CHSs, SjCHS1 increased the (2 S)-naringenin titer by 48.38% in shaking flasks. Finally, we combined the native precursor pathways optimization with the higher-active CHS that screened, and further increased the (2 S)-naringenin titer to 203.49 mg/L from glucose in shaking flasks. The results achieved in this study indicated that plants rich in flavonoids are good sources for higher-active CHS screening, and that the heterologous pathway and chassis precursor flux should be synergistically engineered to achieve higher production.