The ultimate step in the formation of thebaine, a pentacyclic opiate alkaloid readily converted to the narcotic analgesics codeine and morphine in the opium poppy, has long been presumed to be a spontaneous reaction. We have detected and purified a novel enzyme from opium poppy latex that is capable of the efficient formation of thebaine from (7S)-salutaridinol 7-O-acetate at the expense of labile hydroxylated byproducts, which are preferentially produced by spontaneous allylic elimination. Remarkably, thebaine synthase (THS), a member of the pathogenesis-related 10 protein (PR10) superfamily, is encoded within a novel gene cluster in the opium poppy genome that also includes genes encoding the four biosynthetic enzymes immediately upstream. THS is a missing component that is crucial to the development of fermentation-based opiate production and dramatically improves thebaine yield in engineered yeast.

蒂巴因的形成的最终步骤是很容易被认为是自发反应，蒂巴因是一种五环鸦片生物碱，很容易在罂粟中转化为麻醉性止痛药可待因和吗啡。我们已经从鸦片罂粟胶乳中检测和纯化了一种新型酶，该酶能够从（7 S）-salutaridinol 7- O有效形成蒂巴因-乙酸盐以不稳定的羟基化副产物为代价，其优先通过自发的烯丙基消除而产生。值得注意的是，与发病机理相关的10个蛋白质（PR10）超家族的成员蒂巴因合酶（THS）在罂粟基因组中的一个新基因簇内编码，该簇还包括紧邻上游编码四种生物合成酶的基因。THS是缺少的成分，对于开发基于发酵的阿片制剂至关重要，并能显着提高工程酵母中的蒂巴因产量。