STTR Phase I: Cloning of the Diterpene Cyclase Involved in Pseudopterosin/Seco-Pseudopterosin Biosynthesis

这项小型企业技术转让（STTR）第一阶段项目描述了一种与商业相关的可持续生产方法的发展，这种方法是一种抗炎剂，伪蝶蛋白家族。这些化合物和相关的次级假珊瑚素是从柳珊瑚中分离出来的，并在各种体外和体内模型中显示出有希望的活性。甲氧蝶呤（Methopterosin）是伪蝶呤A的甲基醚，作为局部抗炎药已通过I期和II期临床试验取得进展。目前，这些化合物的唯一来源是从珊瑚礁收集的生物质的提取。本研究的目的是对参与这些化合物生物合成的天然萜烯合成酶进行纯化和测序，并克隆相应的基因。这将是首次从海洋生物中克隆出萜烯合成酶。海洋天然产物如伪蝶蛋白和次伪蝶蛋白代表了令人兴奋的治疗剂的新来源。假蝶蛋白的作用机制是新颖的，这表明这些海洋天然产物代表了一类新的抗炎药物，作为化妆品添加剂具有商业市场和未来的临床市场。

This Small Business Technology Transfer (STTR) Phase I Project describes the development of a commercially relevant sustainable production method of a family of anti-inflammatory agents, the pseudopterosins. These compounds and the related seco-pseudopterosins are isolated from the gorgonian coral, Pseudopterogorgia elisabethae, and shown to have promising activity in various in vitro and in vivo models. Methopterosin, the methyl ether of pseudopterosin A, has progressed through Phase I and II clinical trials as a topical antiinflammatory agent. Currently, the only source of these compounds is from extractions of biomass collected from reefs. The aim of the work described is to purify and sequence the native terpene synthase involved in the biosynthesis of these compounds and clone the corresponding gene. This would represent the first cloning of a terpene synthase from any marine organism. Marine natural products such as the pseudopterosins and seco-pseudopterosins represent an exciting new source of therapeutic agents. The mechanism of action of the pseudopterosins appears to be novel suggesting that these marine natural products represent a new class of anti-inflammatory drugs with a commercial market as a cosmetic additive and a future clinical market.