Altering 15-Lipoxygenases to 18-Lipoxygenases and Their Application to the Production of 5,18-Dihydroxyeicosapentaenoic Acids.

ABSTRACT: Resolvin E2 (RvE2), 5S,18R-dihydroxyeicosapentaenoic acid (5S,18R-DiHEPE), and 18S-RvE2 (5S,18S-DiHEPE) are specialized pro-resolving mediators that function in the resolution of inflammation. These SPMs have been produced in trace amounts from eicosapentaenoic acid (EPA) using acetylated cyclooxygenase-2 or cytochrome P450 and 5-lipoxygenase (5-LOX) via 18R- and 18S-hydroxyeicosapentaenoic acid (18R- and 18S-HEPE) intermediates. In this study, we engineered 15R-LOX from Sorangium cellulosum and 15S-LOX from Archangium violaceum into 18R-LOX (L423W/L424M/L568M variant of 15R-LOX) and 18S-LOX (L429W/L430M/L575M variant of 15S-LOX), respectively, via structure-guided enzyme engineering. The engineered 18R-LOX converted EPA into 72.5% 18R-HEPE and 27.5% 15R-HEPE, while the engineered 18S-LOX

SUBMITTER: Lee J 

PROVIDER: S-EPMC12152508 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature