锌指蛋白及人工锌指蛋白对微生物代谢影响的研究进展

Effects of zinc-finger proteins and artificial zinc-finger proteins on microbial metabolisms – a review

摘要:

锌指蛋白由于锌指结构域序列相对保守，识别DNA序列具有高度特异性，所以成为研究较广泛的DNA结合蛋白，但目前对锌指蛋白的研究多集中在真核细胞，而对微生物锌指蛋白，尤其是原核微生物锌指蛋白的研究相对较少。本文综述了近年来微生物锌指蛋白，尤其是原核微生物锌指蛋白的发现及功能的最新研究进展，以及人工锌指蛋白技术在微生物菌株改造中的应用。特定人工锌指蛋白不仅可调控微生物细胞中多基因控制的复杂性状，例如，耐热性、乙醇和丁醇耐性，渗透胁迫耐受性等，还可以利用锌指结构域构建DNA脚手架系统，进而构建复合酶系统，从而提高催化效率和代谢物产量。目前报道的用于微生物代谢调控的人工锌指蛋白利用的都是哺乳动物的基因，未来根据不同微生物中天然锌指蛋白的序列进行人工锌指的设计，将拓展人工转录因子技术在微生物全局基因表达调控中的应用。

Abstract:

Zinc-finger proteins have been widely studied due to their highly conserved structures and DNA-binding specificity of zinc-finger domains. However, researches on the zinc-finger proteins from microorganisms, especially those from prokaryotes, are still very limited. This review focuses on the latest progress on microbial zinc-finger proteins, especially those from prokaryotes and the application of artificial zinc-finger proteins in the breeding of robust strains. Artificial zinc-finger proteins with transcriptional activation or repression domain can regulate the global gene transcription of microbial cells to acquire improved phenotypes, such as stress tolerance to heat, ethanol, butanol, and osmotic pressure. Using the zinc-finger domain as DNA scaffold in the construction of enzymatic system can enhance the catalytic efficiency and subsequently the production of specific metabolites. Currently, zinc-finger domains used in the construction of artificial transcription factor are usually isolated from mammalian cells. In the near future, novel transcription factors can be designed for strain development based on the natural zinc-finger domains from different microbes, which may be used to regulate the global gene expression of microbial cells more efficiently.