초록
<P>Flavonoids are an important class of plant polyphenols that possess a variety of health benefits. In this work, <I>S. cerevisiae</I> was metabolically engineered to produce the flavonoid naringenin, using tyrosine as the precursor. Our strategy to improve naringenin production comprised three modules. In module 1, we employed a modified <I>GAL</I> system to overexpress the genes of the naringenin biosynthesis pathway and investigated their synergistic action. In module 2, we simultaneously up-regulated acetyl-CoA production and down-regulated fatty acid biosynthesis in order to increase the precursor supply, malonyl-CoA. In module 3, we engineered the tyrosine biosynthetic pathway to eliminate the feedback inhibition of tyrosine and also down-regulated competing pathways. It was found that modules 1 and 3 played important roles in improving naringenin production. We succeeded in producing up to ∼90 mg/L of naringenin in our final strain, which is a 20-fold increase as compared to the parental strain.</P><P><B>Graphic Abstract</B><BR><IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jafcau/2017/jafcau.2017.65.issue-31/acs.jafc.7b02507/production/images/medium/jf-2017-02507u_0005.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jf7b02507'>ACS Electronic Supporting Info</A></P>