Controlled formation of mono- and dihydroxy-resolvins from EPA and DHA using soybean 15-lipoxygenase

Resolvins and protectins are important anti-infl am- matory and pro-resolution compounds derived from the enzymatic oxidation of omega-3 fatty acids all -cis -5,8,11,14,17- eicosapentaenoic acid (EPA) and all -cis -4,7,10,13,16,19-doco- sahexaenoic acid (DHA). We have developed a simple, controlled method to synthesize an array of resolvin and pro- tectin analogs from fatty acid starting materials using soybean 15-lipoxygenase. The conditions were optimized for the pro- duction of both mono- and dihydroxy derivatives, with en- zyme concentration and pH found to have a signifi cant effect on the reaction products. The methods were applied to fi biologically important omega-3 and omega-6 fatty acid sub- strates. Mono- and dihydroxy compounds were successfully synthesized from all substrates and the products were char- acterized by normal phase (NP) HPLC , GC-MS, TOF-MS, UV-visible (UV-vis) spectroscopy, and NMR spectroscopy. The methods could be further applied to any polyunsaturated fatty acids containing the cis -1,4,7,10-undecatetraene moiety to produce a range of novel compounds with potential bio- logical activity. —Dobson, E. P., C. J. Barrow, J. A. Kralovec, and J. L. Adcock. Controlled formation of mono- and dihydroxy- resolvins from EPA and DHA using soybean 15-lipoxygenase. J. Lipid Res. 2013. 54: 1439-1447.