Efficient biotransformation of docosahexaenoic acid-rich oils into the lipid mediator resolvin D5 by cells expressing 15S-lipoxygenase using a bioreactor

Resolvin D5 (RvD5), 7S,17S-dihydroxy-4Z,8E,10Z,13Z,15E,19Z-docosahexaenoic acid (DHA) is a specialized pro-resolving mediator (SPM) generated in human macrophages. It is implicated in the resolution of inflammation and synthesized using an inefficient chemical process. Here, DHA-enriched oil hydrolysate was prepared from oils by lipase with resin treatment and solvent extraction. The reaction factors on the biotransformation of oil hydrolysate into RvD5 were optimized using Escherichia coli expressing arachidonate double-oxygenating 15S-lipoxygenase. After optimization, the cells converted 5.0 mM (1.64 g/L) DHA in oil hydrolysate into 4.0 mM (1.44 g/L) RvD5 in a bioreactor for 3.0 h, which was 15-fold higher than that in a flask before optimization, and RvD5 with a purity of > 97% was prepared from reaction solution by treatments of resins. This is the first trial for the production of C22-dihydroxy fatty acid using a bioreactor. This study will contribute to the large-scale production of SPMs from oils.