Systematically Engineered Fatty Acid Catabolite Pathway for the Production of (2 S )-Naringenin in Saccharomyces cerevisiae .

The (2 S )-naringenin is an important natural flavonoid with several bioactive effects on human health. It is also a key precursor in the biosynthesis of other high value compounds. The production of (2S)-naringenin is significantly influenced by the acetyl-CoA available in the cytosol. In this study, we increased the acetyl-CoA supply via the β-oxidation of fatty acids in the peroxisomes of Saccharomyces cerevisiae . Several lipases from different sources and PEX11 , FOX1 , FOX2 , and FOX3 , the key genes of the fatty acid β-oxidation pathway, were overexpressed during the production of (2 S )-naringenin in yeast. The level of acetyl-CoA was 0.205 nmol higher than that in the original strain and the production of (2 S )-naringenin increased to 286.62 mg/g dry cell weight when PEX11 was overexpressed in S. cerevisiae strain L07. Remarkable (2 S )-naringenin production (1129.44 mg/L) was achieved with fed-batch fermentation, with the highest titer reported in any microorganism. Our results demonstrated the use of fatty acid β-oxidation to increase the level of cytoplasmic acetyl-CoA and the production of its derivatives.