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操纵IME4表达,这是Saccharomyces cerevisiae中代谢工程的全球调节策略

Jianxun Zhu¹, Tianyue An², Wenlong Zha¹

¹State Key Laboratory of Bioactive Substance and Function of Natural Medicines, CAMS Key Laboratory of Enzyme and Biocatalysis of Natural Drugs, and NHC Key Laboratory of Biosynthesis of Natural Products, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

Acta pharmaceutica Sinica. B

|July 10, 2023

概括

通过了解RNA调节,可以改善天然产品的代谢工程. 过度表达酵母IME4基因可增强价值化合物的产生,如异oprenoids和芳香化合物.

科学领域:

合成生物学合成生物学
分子生物学分子生物学
生物技术是生物技术.

背景情况:

代谢工程旨在生产天然的药物分子,但由于对代谢网络调节的不完全理解而受到限制.
RNA的修改,如N6-甲基氨酸 (m6A),是基因表达的关键调节者.
在生物生产的微生物细胞工厂中m6A的作用仍然在很大程度上未被探索.

研究的目的:

研究N6-甲基氨酸 (m6A) 修改对Saccharomyces cerevisiae中的代谢途径的影响.
为了确定与化学生产相关的关键生物合成途径中涉及的m6A修饰基因.
评估操纵m6A修饰的潜力,以提高有价值化合物的产生.

主要方法:

使用m6A-RIP-seq或类似技术识别 haploid Saccharomyces cerevisiae 基因组中的m6A峰值.
基因表达变化的量化,以应对IME4的过度表达,酵母m6A甲基转移酶.
对代谢途径活性的分析,重点是糖解,乙-CoA合成和芳香氨基酸合成.
在IME4过度表达后测量异oprenoid和芳香化合物标位.

主要成果:

在Saccharomyces cerevisiae的1151个基因中确定了1470个假定的m6A峰值.
过度表达IME4显著改变了重要代谢途径中的94个基因的转录水平.
具体来说,IME4过度表达增加了糖解,乙-CoA合成和石基酸盐通路中的mRNA基因水平.
参与乙-CoA合成的关键基因ACS1和ADH2通过转录因子被上调.
观察到异oprenoids 和芳香化合物的生产标位显著增加.

结论:

N6-Methyladenosine (m6A) 修改代表了代谢网络中的新型调节层.
酵母IME4基因编码m6A甲基转移酶,可以被操纵以提高特定代谢模块的产生.
针对m6A修饰提供了一种有前途的策略,用于改善类和化合物的生物生产.

关键词:

芳香化合物是一种芳香化合物.异oprenoids 是一种异oprenoids 的类型.代谢工程是代谢工程.在RNA m6A修改的过程中.这种植物是Saccharomyces cerevisiae.

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