Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea.
Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea.
Prog Lipid Res. 2017 Apr;66:50-68. doi: 10.1016/j.plipres.2017.04.003. Epub 2017 Apr 7.
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), arachidonic acid (20:4), and eicosapentaenoic acid (20:5) 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.
前列腺素(PGs)属于类二十烷酸的一个子类,根据其环戊烷环的结构和烃结构中双键的数量进行分类。PGs 是重要的脂类介质,参与炎症反应。各种 PG 合成酶(包括前列腺素 H 合酶(PGHS)、15-羟基前列腺素脱氢酶(15-HPGD)、PGES、PGDS、PGFS、PGIS 和血栓素 A 合酶(TXAS))能够从至少含有三个双键的不饱和 C20 脂肪酸(如二同型-γ-亚麻酸(20:3)、花生四烯酸(20:4)和二十碳五烯酸(20:5))中生物合成多种 PGs。这篇综述总结了 PG 合成酶的生化特性、反应机制和活性位点细节。由于 PGs 参与免疫系统,因此了解 PG 合成酶对于设计新型抗炎药物非常重要。还介绍了各种生物体(如哺乳动物、珊瑚、叶状藻(一种红藻)、酵母和真菌)中 PGs 的生物合成。讨论了 PG 合成酶在用于合成 PGs 的微生物系统中的表达。现在,使用表达不饱和脂肪酸产生酶和 PG 合成酶的代谢工程细胞,可以从葡萄糖或甘油生物合成 PGs。