15-Hydroperoxy-PGE2 : Intermediate in Mammalian and Algal Prostaglandin Biosynthesis

Abstract

Arachidonic-acid-derived prostaglandins (PGs), specifically PGE₂ , play a central role in inflammation and numerous immunological reactions. The enzymes of PGE₂ 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 PGE₂ biosynthesis in the red macroalga Gracilaria vermiculophylla that led to the identification of 15-hydroperoxy-PGE₂ , a novel precursor of PGE₂ and 15-keto-PGE₂ . Interestingly, this novel precursor is also produced in human macrophages where it represents a key metabolite in an alternative biosynthetic PGE₂ pathway in addition to the well-established arachidonic acid-PGG₂ -PGH₂ -PGE₂ route. This alternative pathway of mammalian PGE₂ biosynthesis may open novel opportunities to intervene with inflammation-related diseases.

Keywords: biosynthesis; inflammation; natural products; prostaglandins; structure elucidation.