초록
<P>Resveratrol, a plant-derived polyphenolic compound with various health activities, is widely used in nutraceutical and food additives. Herein, combinatorial optimization of resveratrol biosynthetic pathway and intracellular environment of <I>E. coli</I> was carried out. By screening pathway genes from various species and exploring their expression pattern, we initially constructed resveratrol-producing strains. Further targeting at availability of malonyl-CoA through expressing ACC of <I>Corynebacterium glutamicum</I> and antisense inhibiting native <I>fabD</I> significantly increased resveratrol biosynthesis. Transport engineering for resveratrol secretion and molecular chaperones helping for folding heterologous enzymes were employed to improve the intracellular environments in remarkable degrees. By introducing <I>PcTAL</I> of <I>Phanerochaete chrysosporium</I> and tuning expression model of <I>PcTAL</I>, <I>At4CL</I>, and <I>VvSTS</I>, an engineered <I>E. coli</I> produced 57.77 mg/L of resveratrol from <SMALL>L</SMALL>-tyrosine. After integrating the above strategies, resveratrol titer reached to 238.71 mg/L from <SMALL>L</SMALL>-tyrosine. The combinatorial optimization in this study provides a promising strategy to produce valuable natural products in heterologous expression systems.</P><BR>[FIG OMISSION]</BR>