Abstract
Epoxide metabolites from n-3 and n-6 polyunsaturated fatty acids arouse interest thanks to their physiological and pharmacological activities. Their chemical synthesis has significant drawbacks, and enzymes emerge as an alternative with potentially higher selectivity and greener nature. Conversion of eleven eicosanoid, docosanoid, and other n-3/n-6 fatty acids into mono-epoxides by fungal unspecific peroxygenases (UPOs) is investigated, with emphasis on the Agrocybe aegerita (AaeUPO) and Collariella virescens (rCviUPO) enzymes. GC-MS revealed the strict regioselectivity of the n-3 and n-6 reactions with AaeUPO and rCviUPO, respectively, yielding 91%-quantitative conversion into mono-epoxides at the last double bond. Then, six of these mono-epoxides were obtained at mg-scale, purified and further structurally characterized by 1H, 13C and HMBC NMR. Moreover, chiral HPLC showed that the n-3 epoxides were also formed (by AaeUPO) with total S/R enantioselectivity (ee > 99%) while the n-6 epoxides (from rCviUPO reactions) were formed in nearly racemic mixtures. The high regio- and enantioselectivity of several of these reactions unveils the synthetic utility of fungal peroxygenases in fatty acid epoxidation.
Highlights
The same mono-epoxide was formed by rCciUPO (Figure 3B) but hydroxylated EPA derivatives were observed
Assigned following the elution order of related epoxides since no standards are available. These results reveal that A. aegerita UPO (AaeUPO) is a powerful tool to get access to mono-epoxides of n-3 fatty acids with high conversion (>99%), regioselectivity (>90%) and total enantioselectivity towards the S/R enantiomers
When analyzing mono-epoxidation of a series of n-3 and n-6 polyunsaturated fatty acids by several unspecific peroxygenases (UPOs), high conversions (93%-quant) and regioselectivities (91%-quant) towards the last double bond were accomplished with AaeUPO and rCviUPO (Scheme 1)
Summary
Epoxylipids include a series of epoxide metabolites from n-3 and n-6 ( known as omega 3 and omega 6) polyunsaturated eicosanoid and docosanoid acids, among others, that play important roles in a range of biological processes [1]. These compounds are mediators in the inflammatory response [2] and are involved in the regulation of blood pressure [3], pain perception [4], and angiogenesis [5]. Epoxylipids are strongly linked to the endothelial system as well as to organs such as heart and kidney, contributing to controlling hypertension and cardiovascular diseases [6,7,8]
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