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基于酵母的N-脱甲基化,用于在料批量或连续栽培中生产诺里帕

Siyi Xue¹, Xu Li¹, Daniel Yaw¹

¹Department of Chemical Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia; The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia.

Bioresource technology

|November 20, 2025

概括

研究人员开发了一种新的生物转化工艺,使用昆虫衍生的N-甲基酶产生诺里帕,这是布普伦诺芬合成的关键中间体. 这种环保方法为治疗性类化合物的传统化学合成提供了可扩展和高效的替代方案.

科学领域:

生物技术是生物技术.
生物催化剂是一种生物催化剂.
合成生物学合成生物学

背景情况:

目前用于合成阿片类成治疗中必不可少的药物 - - 布普伦诺芬的合成方法是不理想的.
生物转化为合成诸如布普伦诺芬之类的治疗性类化合物提供了潜在的替代途径.
有效的N-脱甲基化需要一个特定的N-脱甲基酶和一个可扩展的生物工艺.

研究的目的:

确定和描述一种新型N-脱甲基酶,能够有效地将oripavine转化为nororipavine.
开发和优化一个全细胞生物转化过程,用于Saccharomyces cerevisiae中的诺里帕生产.
评估化物合成开发的生物转化工艺的可扩展性和工业潜力.

主要方法:

来自来自昆虫害虫的N-脱甲基酶,它们以含有oripavine的植物为食.
在Saccharomyces cerevisiae中表达了N-脱甲基酶,与细胞染色体P450氧化还原酶和精氨酸浸透酶相结合.
使用批量,料批量和连续加工模式研究生物转化动力学和产量.

主要成果:

通过工程酵母系统,成功将N-脱甲基化oripavine转化为nororipavine.
通过食批量细胞生长和批量生物转化,通过食批量细胞生长和批量生物转化达到1.59 g/L的最高标位.
在使用连续加工的0.7L尺度下,表现出1.01g/L/day的生产率.

结论:

这项研究提出了一种新的,环保的,工业上可扩展的全细胞生物转化方法,用于高价值的基素类化合物.
开发的N-脱甲基化过程显示了优化布普伦诺芬前体生产的巨大潜力.
进一步优化酶和生物过程,特别是连续加工,可以提高治疗性类化合物合成的产量和生产率.

关键词:

化素化物化素化物生物反应器是一种生物反应器.生物转化生物转化在阿片类药物中,阿片类药物奥里帕维尼 (Oripavine) 是一种葡萄.这种植物是Saccharomyces cerevisiae.合成生物学合成生物学

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