ArticleBiotechnology and bioengineering2025
Altering 15-Lipoxygenases to 18-Lipoxygenases and Their Application to the Production of 5,18-Dihydroxyeicosapentaenoic Acids.
Article in Biotechnology and bioengineering, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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 formed 81.8% 18S-HEPE and 18.2% 15S-HEPE. Escherichia coli expressing the engineered 18R- or 18S-LOX converted 4.0 or 3.0 mM EPA into 2.0 mM (641 mg/L) 18R-HEPE or 1.8 mM (577 mg/L) 18S-HEPE in 20 min, respectively, achieving concentrations that were > 10
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