Abstract
Resveratrol is a plant secondary metabolite with multiple health-beneficial properties. Microbial production of resveratrol in model microorganisms requires extensive engineering to reach commercially viable levels. Here, we explored the potential of the non-conventional yeast Yarrowia lipolytica to produce resveratrol and several other shikimate pathway-derived metabolites (p-coumaric acid, cis,cis-muconic acid, and salicylic acid). The Y. lipolytica strain expressing a heterologous pathway produced 52.1 ± 1.2 mg/L resveratrol in a small-scale cultivation. The titer increased to 409.0 ± 1.2 mg/L when the strain was further engineered with feedback-insensitive alleles of the key genes in the shikimate pathway and with five additional copies of the heterologous biosynthetic genes. In controlled fed-batch bioreactor, the strain produced 12.4 ± 0.3 g/L resveratrol, the highest reported titer to date for de novo resveratrol production, with a yield on glucose of 54.4 ± 1.6 mg/g and a productivity of 0.14 ± 0.01 g/L/h. The study showed that Y. lipolytica is an attractive host organism for the production of resveratrol and possibly other shikimate-pathway derived metabolites.
Highlights
Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a stilbenoid natu rally present in grapes, berries, Japanese knotweed, and peanuts (Burns et al, 2002)
We have investigated the potential of Y. lipolytica for the production of several shikimate pathway-derived metabolites: p-cou maric acid, resveratrol, cis,cis-muconic acid, and salicylic acid
The pathway was further extended up to resveratrol with At4CL1 from Arabidopsis thaliana and VvVST1 from Vitis vinifera, genes that were successfully expressed in S. cerevisiae (Li et al, 2015)
Summary
Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a stilbenoid natu rally present in grapes, berries, Japanese knotweed, and peanuts (Burns et al, 2002). In plants, it serves as phytoalexin, produced in defense against injuries and microbial infections (Langcake and Pryce, 1976; Vestergaard and Ingmer, 2019). Extraction from Japanese knot weed remains the main source of resveratrol, but chemical synthesis by DSM and microbial fermentation by Evolva are gaining ground in the market (DSM, 2014; Evolva, 2019; Future Market Insights, 2019). Mi crobial fermentation process of resveratrol production has a number of advantages, such as low cost, high purity of the product, and indepen dence on season
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have