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一个强大的酵母生物控制系统,具有双层调节开关,依赖于非自然氨基酸

Tiantian Chang^1,2, Weichao Ding^1,2,3,4, Shirui Yan^2,3,4

¹College of Life Sciences, University of Chinese Academy of Sciences, 100049, Beijing, China.

Nature communications

|October 14, 2023

概括

合成辅食性限制了转基因酵母,因为它需要非天然的氨基酸才能生存. 这种强大的生物控制策略可以防止不必要的传播,并保护工业菌株.

科学领域:

合成生物学合成生物学
生物技术是生物技术.
微生物遗传学微生物遗传学

背景情况:

合成辅助营养依赖于非自然氨基酸 (unAAs) 进行细胞活力,提供一种控制转基因生物 (GMO) 的方法.
防止转基因生物逃逸和工业间活动对于开放环境和专有菌株至关重要.

研究的目的:

开发一种通用且强大的生物封闭策略,用于使用合成辅的开花酵母.
设计具有增强抵抗逃脱机制的酵母菌株,并实施转录和转化生物控制开关.

主要方法:

针对珀抑制器tRNA的设计"免疫力"以防止逃逸.
开发了基于转录和转化的生物控制开关.
采用以健身为导向的选方法,以获得具有无法检测的逃逸频率 (<~10^-9) 的多重防护菌株.

主要成果:

在依赖unAAs的芽酵母中实现了强大的生物封闭.
开发了多重防护菌株,呈现出高生长率和极低逃脱率.
在真实发酵场景中证明有效地限制了菌株的扩散.

结论:

开发的多重防护系统为酵母生物控制提供了一个强有力的战略.
这种方法显著提高了工业专利酵母菌株的保护.
该战略的通用性具有广泛应用在转基因生物制约领域的潜力.

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