Journal article
Engineering the oleaginous yeast Yarrowia lipolytica for high-level resveratrol production
Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark1
Synthetic Biology Tools for Yeast, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark2
Yeast Metabolic Engineering, Research Groups, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark3
Research Groups, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark4
Pre-Pilot Plant, Translational Management, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark5
Technical University of Denmark6
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.
Language: | English |
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Publisher: | Academic Press |
Year: | 2020 |
Pages: | 51-61 |
ISSN: | 10967184 and 10967176 |
Types: | Journal article |
DOI: | 10.1016/j.ymben.2020.08.009 |
ORCIDs: | Saez Saez, Javier , Marella, Eko Roy , Borodina, Irina and 0000-0001-7459-2326 |