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Oxygenation of polyunsaturated fatty acids with molecular oxygen by fatty acid dioxygenases (cyclooxygenases and lipoxygenases) is used as the first step in the biosynthesis of cell hormones and chemical messengers, as prostaglandins and leukotrienes in animals, and jasmonic acid derivatives in plants. Our recent studies established that cyclooxygenase (COX) pathway of prostaglandin synthesis is not representative of vertebrate animals only, but is common to marine invertebrates also. Moreover, our preliminary studies indicate that a COX-related enzyme is involved in prostaglandin synthesis in the red alga Gracilaria asiatica. The aims of the present grant proposal are to elucidate the algal pathway of prostaglandin biosynthesis, to clone and express the first COX of non-animal origin, and to compare its structure and catalytical properties with these of known animal COXes. In addition to an evolutionary standpoint, comparative structure-function studies of COXes from organisms of different scale help to explain differences in expression, catalytical and inhibition characteristics between human COX isozymes, important in design of efficient and safe anti-inflammatory and anti-cancer dugs. The establishment of prostaglandin biosynthesis in the alga G. asiatica could help to explain severe human intoxications caused by eating this popular seaweed in Japan. |