Neopinone isomerase is involved in codeine and morphine biosynthesis in opium poppy
Neopinone isomerase is involved in codeine and morphine biosynthesis in opium poppy
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DOI：
10.1038/s41589-019-0247-0
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发表时间：
2019-04-01
影响因子：
14.8
通讯作者：
Facchini, Peterj
中科院分区：
文献类型：
--
作者：
Dastmalchi, Mehran;Chen, Xue;Facchini, Peterj
新酮异构化为可待因酮是罂粟中阿片类生物碱生物合成的关键步骤。以前认为是自发的，这个过程实际上是由新酮异构酶（NISO）催化的。在没有NISO的情况下，植物、工程微生物和体外的主要代谢产物是neopine和neomorphine，它们分别是可待因和吗啡的结构异构体。将NISO包含在被工程化以将蒂巴因转化为天然或半合成阿片类药物的酵母菌株中，以neopine和neomorphine积累为代价显著增强了所需产物的形成。沿着蒂巴因合成酶，NISO是发病相关蛋白10（PR10）家族的第二个成员，最近涉及吗啡生物合成中假定的自发转化的酶催化。
The isomerization of neopinone to codeinone is a critical step in the biosynthesis of opiate alkaloids in opium poppy. Previously assumed to be spontaneous, the process is in fact catalyzed enzymatically by neopinone isomerase (NISO). Without NISO the primary metabolic products in the plant, in engineered microbes and in vitro are neopine and neomorphine, which are structural isomers of codeine and morphine, respectively. Inclusion of NISO in yeast strains engineered to convert thebaine to natural or semisynthetic opiates dramatically enhances formation of the desired products at the expense of neopine and neomorphine accumulation. Along with thebaine synthase, NISO is the second member of the pathogenesis-related 10 (PR10) protein family recently implicated in the enzymatic catalysis of a presumed spontaneous conversion in morphine biosynthesis.