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在非传统酵母中改进小分子剂的同质导向修复,用于基因工程? - - 从哺乳动物系统的工程学习

Min Lu¹, Sonja Billerbeck¹

¹Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands.

Microbial biotechnology

|February 20, 2024

概括

小分子可以通过促进同源重组 (HR) 而不是非同源末端连接 (NHEJ) 来增强酵母中的基因组编辑. 这项研究审查了改善酵母基因工程和选方法的化学物质.

科学领域:

分子生物学分子生物学
合成生物学合成生物学
酵母遗传学酵母遗传学

背景情况:

精确的基因组编辑对于研究生物功能和开发细胞工厂至关重要.
许多酵母,包括致病性和工业菌株,偏好非同源端结合 (NHEJ) 而不是同源重组 (HR),阻碍了基因操纵.
调节哺乳动物细胞中DNA修复通路的化学物质为提高酵母中的HR提供了潜在的策略.

研究的目的:

巩固对增强哺乳动物细胞和酵母菌同类重组 (HR) 效率的小分子的知识.
探索化学剂在改善酵母中的基因组编辑方面的潜力.
确定用于选NHEJ/HR的酵母特异性抑制剂的高通量试验.

主要方法:

对用于改善哺乳动物细胞和酵母细胞HR的小分子的文献综述.
关于参与DNA修复途径的保存蛋白标知识的汇编.
包括可用的高通量兼容的NHEJ/HR量化试验用于选.

主要成果:

确定了调节哺乳动物细胞NHEJ和HR通路的小分子.
强调了这些化学剂在酵母工程中的有限应用.
提交了相关的高通量测试,用于选酵母特异性抑制剂.

结论:

化学增强HR为酵母工程提供了一个有希望的,但尚未被探索的途径.
保存的蛋白质标表明,有可能将基于哺乳动物细胞的小分子重新用于酵母.
开发和应用酵母特异性选试验对于推进HR介导的基因组编辑至关重要.

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