In vivo production of psilocybin in E. coli
In vivo production of psilocybin in E. coli
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DOI：
10.1016/j.ymben.2019.09.009
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发表时间：
2019-12-01
影响因子：
8.4
通讯作者：
Jones, J. Andrew
中科院分区：
文献类型：
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作者：
Adams, Alexandra M.;Kaplan, Nicholas A.;Jones, J. Andrew
裸盖菇素是精神活性分子裸盖菇素的前药，在治疗成瘾、抑郁症和创伤后应激障碍的临床试验中显示出有希望的结果。在高度工程化的微生物中开发裸盖菇素生产平台可能会导致用于正在进行的临床试验的裸盖菇素生物生产的快速进展。在这里，我们展示了模型微生物大肠杆菌中模块化生物合成生产平台的开发。对使用多种遗传优化技术优化和改善途径性能的努力进行了评估，结果使裸盖菇素滴度提高了 32 倍。通过发酵优化，进一步增强了这种遗传优势菌株，最终进行了补料分批发酵研究，裸盖菇素的生产滴度为 1.16 g/L。这是迄今为止从重组生物中获得的最高裸盖菇素滴度，也是向证明生物来源裸盖菇素工业化生产的可行性迈出的重要一步。
Psilocybin, the prodrug of the psychoactive molecule psilocin, has demonstrated promising results in clinical trials for the treatment of addiction, depression, and post-traumatic stress disorder. The development of a psilocybin production platform in a highly engineerable microbe could lead to rapid advances towards the bioproduction of psilocybin for use in ongoing clinical trials. Here, we present the development of a modular biosynthetic production platform in the model microbe, Escherichia coli. Efforts to optimize and improve pathway performance using multiple genetic optimization techniques were evaluated, resulting in a 32-fold improvement in psilocybin titer. Further enhancements to this genetically superior strain were achieved through fermentation optimization, ultimately resulting in a fed-batch fermentation study, with a production titer of 1.16 g/L of psilocybin. This is the highest psilocybin titer achieved to date from a recombinant organism and a significant step towards demonstrating the feasibility of industrial production of biologically-derived psilocybin.