Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a stilbene compound naturally found in grapes, berries, knotweed and peanuts, which acts as a plant antitoxin. Can help plants defend against damage and microbial infections. In recent years, more and more studies have shown that it has strong antioxidant, anti-tumor, and anti-cancer effects. There are also clinical trials that prove that resveratrol has significant effects on improving diabetes, cardiovascular diseases and neurological diseases. Resveratrol has great potential and market prospects as a drug development. Scientists are committed to producing resveratrol through metabolic engineering of microorganisms.
Recently, the research team of Irina Borodina of the Technical University of Denmark found that Yarrowia lipolytica has sufficient malonyl-CoA in its body, which is a better natural synthetic host for phenylpropanes. The team integrated tyrosine ammonia lyase, 4-coumarin-CoA ligase, and resveratrol synthase genes into Yarrowia lipolytica to make it initially capable of resveratrol synthesis. In order to further increase the yield, the team found feedback-insensitive variants of key genes of the shikimate pathway, relieved the feedback inhibition of L-tyrosine, and increased the copy number of the three key enzyme genes to 5 at the same time. The C/N ratio and fermentation conditions were optimized, and the results of fed-batch fermentation showed that the output of resveratrol could reach 12.4±0.3 g/L, which was the highest reported titer for de novo synthesis of resveratrol so far.
This study shows the great potential of Yarrowia lipolytica as a host for resveratrol and other derivatives of the shikimic acid pathway.
Link to the paper:https://doi.org/10.1016/j.ymben.2020.08.009