Enzymatic synthesis of new hepoxilins and trioxilins from polyunsaturated fatty acids Electronic supplementary information (ESI) available. See DOI: 10.1039/c9gc01031a

Abstract

Hepoxilins (HXs) and trioxilins (TrXs) are lipid mediators that regulate diverse physiological processes at trace amounts in humans. They have been synthesized by chemical methods, which have disadvantages such as low yield, byproduct formation, and use of toxic chemical reagents. Here, we reported the identification of ten types of HXs and TrXs synthesized by recombinant Escherichia coli expressing bacterial arachidonate 15-lipoxygenase and/ or epoxide hydrolase using five polyunsaturated fatty acids (PUFAs). Of these, eight types were new. The discovery was due to the microbial enzymes with high activities for the same catalytic activities as those of human enzymes. We succeeded in the efficient, cost-effective, and environmentally friendly biotransformation of PUFAs into nine types of HXs and TrXs by cells, yielding > 10 g L-1 of 14,15-HXB3 and 13,14,15-TrXB3, with conversion yields of > 70%. Our study contributes to the environmentally friendly synthesis of medicinally important lipid mediators.