TetR家族转录调控因子配体的研究进展

Ligands of TetR family transcriptional regulators: a review

摘要:

TetR家族转录调控因子 (TetR family transcriptional regulators，TFRs) 广泛分布于细菌与古菌中，最早被发现的是可控制大肠杆菌四环素外排泵的TetR。TFRs拥有DNA结合和多样的配体感知能力，其作用机制复杂。配体小分子诱导TFRs产生构象变化，抑制或促进TFRs对其靶点的控制。目前已知的TFRs配体种类繁多，包括糖类、蛋白质、脂肪酸及其衍生物、金属离子等。配体的多样性使得TFRs调节范围很广，包括从基础碳代谢、氮代谢到群体感应、抗生素生物合成等一系列生理过程。文中主要从介导调控角度介绍TFRs配体的研究进展，并结合笔者实验室的研究工作，重点阐述TFRs配体在基础碳代谢、脂肪酸生物合成与降解等初级和次级代谢产物合成过程中的作用机制，及其在基因线路开发和抗生素合成基因的激活等应用方面的研究进展。

关键词:细菌，古菌，TetR家族转录因子，配体，反馈调控，前馈控制

Abstract:

TetR family transcriptional regulators (TFRs) are widely distributed in bacteria and archaea, and the first discovered TFR was confirmed to control the expression of tetracycline efflux pump in Escherichia coli. TFRs can bind DNAs and ligands. Small molecule ligands can induce conformational changes of TFRs, inhibiting or promoting TFRs to control target gene expression. Currently, TFRs have a wide variety of ligands, including carbohydrates, proteins, fatty acids and their derivatives, metal ions, and so on. Due to the diversity of ligands, TFRs regulate a wide range of physiological processes, from basic carbon metabolism and nitrogen metabolism to quorum sensing and antibiotic biosynthesis. On the basis of the recent studies in our laboratory and the literature, we review here the regulatory mechanism mediated by ligands of TFRs in primary and secondary metabolism, as well as the application of ligands for TFRs in the development of gene route and the activation of antibiotic biosynthesis.

Key words:bacteria, archaea, TetR family transcription factors, ligand, feedback regulation, feed-forward control