Biosynthetic engineering of isoquinoline alkaloids in microbes

为了提高生物碱在我们的微生物系统中的生产效率，我们修改了生物合成途径，建立了细胞色素P450在大肠杆菌细胞中的表达体系。这些结果使大肠杆菌细胞能够产生大量的生物碱。从罂粟中分离到合成基因，并在大肠杆菌细胞中表达，用于生产药用重要生物碱麻醉剂。我们培育了一株能产生特巴因的大肠杆菌菌株，将特巴因的生物合成基因引入到产生特巴因的特巴因大肠杆菌细胞中。LC-MS分析表明，培养基中有中间产物积累，但未检测到中间产物。我们已经检查了工厂的生产条件。

To improve the productivity of alkaloids in our microbial system, we modified the biosynthetic pathway and established the cytochrome P450 expression system in E. coli cells. Theses results enable the production of large amounts of alkaloids in E. coli cells. For the production of pharmaceutical important alkaloid narcotic, the biosynthetic genes were isolated from opium poppy, and were expressed in E. coli cells. We generated an E. coli strain that produce thebaine, introducing thebaine biosynthetic genes from reticuline in the reticuline producing E. coli cells. LC-MS analysis showed that the intermediates accumulated in the culture, but thebain was not detected. We have examined the production condition of thebaine.