Prostaglandin synthases: Molecular characterization and involvement in prostaglandin biosynthesis

Abstract

Prostaglandins (PGs) belong to a subclass of eicosanoids and are classified based on the structures of the cyclopentane ring and their number of double bonds in their hydrocarbon structures. PGs are important lipid mediators that are involved in inflammatory response. The biosynthesis of diverse PGs from unsaturated C20 fatty acids containing at least three double bonds such as dihomo-γ-linoleic acid (20:3^Δ8Z,11Z,14Z), arachidonic acid (20:4^{Δ5Z,8Z,11Z,14Z}), and eicosapentaenoic acid (20:5^{Δ5Z,8Z,11Z,14Z,17Z}) is enables by various PG synthases, including prostaglandin H synthase (PGHS), 15-hydroxyprostaglandin dehydrogenase (15-HPGD), PGES, PGDS, PGFS, PGIS, and thromboxane A synthase (TXAS). This review summarizes the biochemical properties, reaction mechanism, and active site details of PG synthases. Because PGs are involved in the immune system, an understanding of PG synthases is important in the design of new anti-inflammatory drugs. The biosynthesis of PGs in various organisms, such as mammals, corals, florideae (a class of red algae), yeast, and fungi, is also introduced. The expression of PG synthases in the microbial systems for the synthesis of PGs is discussed. Now, the biosynthesis of PGs from glucose or glycerol is possible using metabolically engineered cells expressing both unsaturated fatty acid-producing enzymes and PG synthases.