15‐Hydroperoxy‐PGE(2): Intermediate in Mammalian and Algal Prostaglandin Biosynthesis

Arachidonic‐acid‐derived prostaglandins (PGs), specifically PGE(2), play a central role in inflammation and numerous immunological reactions. The enzymes of PGE(2) biosynthesis are important pharmacological targets for anti‐inflammatory drugs. Besides mammals, certain edible marine algae possess a comprehensive repertoire of bioactive arachidonic‐acid‐derived oxylipins including PGs that may account for food poisoning. Described here is the analysis of PGE(2) biosynthesis in the red macroalga Gracilaria vermiculophylla that led to the identification of 15‐hydroperoxy‐PGE(2), a novel precursor of PGE(2) and 15‐keto‐PGE(2). Interestingly, this novel precursor is also produced in human macrophages where it represents a key metabolite in an alternative biosynthetic PGE(2) pathway in addition to the well‐established arachidonic acid‐PGG(2)‐PGH(2)‐PGE(2) route. This alternative pathway of mammalian PGE(2) biosynthesis may open novel opportunities to intervene with inflammation‐related diseases.