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在酵母中生物合成药用类

Prashanth Srinivasan¹, Christina D Smolke^2,3

¹Department of Bioengineering, Stanford University, Stanford, CA, USA.

|September 4, 2020

概括

研究人员利用面包酵母从糖分中制造出必需的类化合物胺和胺. 这种微生物生物合成平台为生产这些重要药物提供了强大的替代方案,克服了全球供应链的脆弱性.

科学领域:

生物技术
代谢工程
制药科学

背景情况:

从夜植物中提取的热类化合物是用于治疗神经肌肉疾病的关键神经递质抑制剂,并被世界卫生组织认定为基本药物.
目前这些重要化合物的全球供应链面临重大挑战,包括澳大利亚野火和COVID-19大流行等事件加剧的短缺.
需要快速部署和适应性强的生产策略,能够抵御环境和社会经济的破坏.

研究的目的:

将面包酵母设计为一种微生物平台,用于生物合成药用类类化合物,特别是胺和胺.
通过开发替代,强大的生产方法来解决全球基本药品供应链的漏洞.
探索微生物生物合成的潜力,以发现用于神经疾病治疗的新型类衍生物.

主要方法:

使用功能性基因组学来识别特罗潘类生物合成途径中缺失的关键酶.
采用蛋白质工程来通过真空运输实现乙烯转移酶的功能表达.
集成的异质转运器以实现有效的细胞内路由,并进行菌株优化以提高类产量.
通过在酵母中的六个亚细胞位点调配来自不同生物的二十多种蛋白质,重建了植物的类生物合成的空间组织.

主要成果:

从简单的糖和氨基酸中成功地制造了面包酵母.
在酵母中开发出多个生物体的蛋白质系统,模仿多个细胞区的植物生物合成途径.
证明了微生物生产必需的类化合物的概念,克服了以前的局限性.

结论:

人工面包酵母为可持续生产必需的类提供了可行且坚固的平台.
这种微生物生物合成方法可以提高药品供应链的灵活性和弹性.
该平台有望发现具有神经疾病治疗潜力的新型类衍生物.

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