细菌警报素(p)ppGpp代谢的关键调控者：RSH蛋白的功能多样性

Functional diversity of RSH proteins, key regulators of bacterial alarmone (p)ppGpp metabolism

摘要:

细菌的严紧反应(stringent response)是细菌在面临恶劣生存环境时，通过改变新陈代谢并降低生长速度，以增强存活和适应环境能力的一种适应性反应。此反应由鸟苷四磷酸(guanosine tetraphosphate, ppGpp)和鸟苷五磷酸(guanosine pentaphosphate, pppGpp) (合称(p)ppGpp)的快速积累所介导，在微生物应对环境变化中发挥关键作用。细菌内的(p)ppGpp水平由RelA/SpoT同源蛋白(RelA/SpoT homologues, RSH)调控，包括小警报素合成酶(small alarmone synthetases, SAS)、小警报素水解酶(small alarmone hydrolases, SAH)以及双功能蛋白Rel。此外，近期研究发现了一种新的细菌警报素腺苷四磷酸(adenosine tetraphosphate, ppApp)和腺苷五磷酸(adenosine pentaphosphate, pppApp) (合称(p)ppApp)，它能调控细菌的多种生物过程。鉴于不同细菌中涉及(p)ppGpp代谢的酶有所不同，本文对已知的RSH蛋白的结构及其生化特性进行系统的分类与综述，并总结其生物学功能，以促进未来在这一领域的深入研究与发展。

关键词:(p)ppGpp;细菌严紧反应;(p)ppApp;RelA/SpoT同源蛋白;核苷酸代谢

Abstract:

The bacterial stringent response refers to the adaptive reaction that bacteria exhibit when faced with adverse environmental conditions, altering their metabolism and reducing the growth rate to enhance survival and adaptability. The rapid accumulation of guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), collectively referred to as (p)ppGpp in this article, mediates the stringent response, playing a crucial role in microbial adaptation to environmental changes. The levels of (p)ppGpp within bacteria are regulated by RelA/SpoT homologue (RSH) proteins, which include small alarmone synthetases (SASs), small alarmone hydrolases (SAHs), and bifunctional proteins such as Rel. Furthermore, recent studies have identified a new bacterial alarmone, adenosine tetraphosphate (ppApp) and adenosine pentaphosphate (pppApp), collectively referred to as (p)ppApp, which is involved in the regulation of various biological processes in bacteria. The enzymes involved in (p)ppGpp metabolism vary among different bacterial species. This study systematically classifies and reviews the structural and biochemical characteristics of the known RSH proteins and summarizes their biochemical functions, aiming to promote further exploration and development in this field.

Key words:(p)ppGpp;bacterial stringent response;(p)ppApp;RelA/SpoT homologue proteins;nucleotide metabolism