Novel transformations of polyunsaturated fatty acids and eicosanoids

Ernst Oliw, Johan Bylund and Tomas Nilsson

Arachidonic acid can be oxygenated to biologically important mediators of fever, pain and inflammation, viz. prostaglandins, leukotrienes and epoxyeicosatrienoic acids (EETs). We focus on the oxygenation of arachidonic acid and eicosanoids by cytochrome P450 4 family enzymes: CYP4F8 (prostaglandin H 19-hydroxylase) and two orphan enzymes, CYP4F22 and CYP4V2. Mutations of two latter have been implicated in retinal and skin diseases and we are now expressing these enzymes in yeasts in order to characterize these enzymes.

Characterization of heme-containing fatty acid dioxygenases and hydroperoxide isomerases of human and plant pathogens

Ernst Oliw, Ulrike Garscha, Fredrik Jernerén, Inga Hoffmann

Fungi are severe pathogens of man and can be devastating for important crops. Aspergillus causes farmer´s lung disease and invasive aspergillosis of immunocompromized patients. Rice blast disease is caused by Magnaporthe grisea, and destroys ~25% of rice crops worldwide. Aspergillus and M. grisea contain cyclooxygenase-related enzymes, diol synthases and dioxygenases, which transform linoleic acid into hydroperoxides and dihydroxy fatty acids. Our aim is to characterize the enzymes by enzyme expression, gene targeting and by studies on their biological importance.

Characterization of oleic acid 7,10-diol synthase of Pseudomonas aeruginosa

Eriel Martínez, Ernst Oliw

P. aeruginosa is a Gram negative pathogen, which transforms oleic acid to a 7,10-dihydroxy metabolite by unknown mechanisms. Our aim is to characterize the reaction mechanism.