吗啡的合成生物学研究和工业化生产  

Progress of biosynthesis of Morphine and its industrial manufacture

作　　者：范楚珧 刘龙英 沈玥 陈泰 曾筱凡 杨焕明[1,2] 

机构地区：[1]深圳华大基因研究院,深圳518083 [2]浙江大学沃森基因组科学研究院,杭州310058

出　　处：《科学通报》2016年第13期1436-1444,共9页Chinese Science Bulletin

基　　金：国家高技术研究发展计划(2012AA02A708)资助

摘　　要：吗啡是鸦片中重要的生物碱,其合成生物学制造及相关工业化生产,是合成生物学领域继人工合成青蒿素之后最有代表性的实例.本文从吗啡合成的有关代谢通路的阐明和设计开始,总结整理吗啡在酵母中的生物合成方法,介绍这一划时代工作的全过程及合成生物学技术的潜力和前景.Benzylisoquinoline alkaloids（BIA） are a diverse family of nitrogen-containing plant-specialized secondary metabolites. Morphine is one subclass of BIAs produced in only a few plant species, which is the most abundant analgesic opiate found in the opium poppy. Morphine has been used as a pain reliever for years and has been classified by WHO（World Health Organization） as an essential medicine due to its use in pain management and palliative care. However, the supply of morphine is not adequate to the demand in the world, especially in the developing areas. The primary source of morphine is the extraction from poppy straw of the opium poppy, but yields are poor because the metabolites accumulate at low levels in plant cells. An alternative way of producing morphine is chemical synthesis, but this way is high-cost and hampered by the complexity and chirality of morphine. As such, the reconstruction of morphine biosynthetic pathways in microorganisms has attracted more and more researchers in recent studies, because microbial systems can improve not only the quantity but also the quality of products. The developments in synthetic biology, combined with continued process in systems biology and metabolic engineering, have enabled the engineering of microorganisms to produce morphine in a manner that was previously unfeasible. And the biosynthesis of morphine is regarded as the most representative example after the successful biosynthesis of artemisinin. A number of recent reports have successfully reconstituted BIA pathways into Saccharomyces. cerevisiae, Escherichia. coli and combinations there of in co-culture systems. According to these reports, we clarified the related metabolic pathways and synthesis design of the morphine biosynthesis in microbial systems in this review. We divided the whole morphine biosynthesis pathway into three modules： module（ⅰ） is the synthesis of L-tyrosine fromsugar; module（ⅱ） is the production of（S）-reticuline from L-tyrosine; and module（ⅲ） is the synthesi

关 键 词：吗啡 酵母 生物合成 合成生物学 工业化生产 

分 类 号：TQ283[化学工程—有机化工]