posted on 2024-01-29, 06:03authored byKaifeng Wang, Yueyue Zhou, Lizhen Cao, Lu Lin, Rodrigo Ledesma-Amaro, Xiao-Jun Ji
Punicic acid is a conjugated linolenic acid with various
biological
activities including antiobesity, antioxidant, anticancer, and anti-inflammatory
effects. It is often used as a nutraceutical, dietary additive, and
animal feed. Currently, punicic acid is primarily extracted from pomegranate
seed oil, but it is restricted due to the extended growth cycle, climatic
limitations, and low recovery level. There have also been reports
on the chemical synthesis of punicic acid, but it resulted in a mixture
of structurally similar isomers, requiring additional purification/separation
steps. In this study, a comprehensive strategy for the production
of punicic acid in Yarrowia lipolytica was implemented by pushing the supply of linoleic acid precursors
in a high-oleic oil strain, expressing multiple copies of the fatty
acid conjugase gene from Punica granatum, engineering the acyl-editing pathway to improve the phosphatidylcholine
pool, and promoting the assembly of punicic acid in the form of triglycerides.
The optimal strain with high oil production capacity and a significantly
increased punicic acid ratio accumulated 3072.72 mg/L punicic acid,
accounting for 6.19% of total fatty acids in fed-batch fermentation,
providing a viable, sustainable, and green approach for punicic acid
production to substitute plant extraction and chemical synthesis production.