核苷类第二信使与放线菌代谢、发育及环境适应的调控机制研究进展

Nucleotide second messengers regulate metabolism, development, and environmental adaptation of actinobacteria: a review

摘要:

放线菌是一类在生态功能和生物技术领域均具有重要地位的革兰氏阳性细菌，它们不仅驱动自然界的有机质循环，还是抗生素及其他生物活性天然产物的主要来源。其复杂的生理适应与生命活动受到精密信号转导系统的调控。本文聚焦于2类代表性放线菌：形态复杂且次级代谢丰富的链霉菌(代表工业生产菌株)以及具备宿主适应性与致病性的分枝杆菌(代表病原类群)，系统综述了核苷类第二信使[包括环二腺嘌呤核苷酸(cyclic diadenosine monophosphate, c-di-AMP)、环二鸟嘌呤核苷酸(cyclic di-guanosine monophosphate, c-di-GMP)、环腺嘌呤核苷酸(adenosine monophosphate, cAMP)及(p)ppGpp]在细胞内的代谢、信号传递及其调控网络。进一步探讨了这些信号分子如何与双组分系统、群体感应及蛋白质酰化修饰等其他调控途径交互作用，从而整合环境与发育信号，协调细菌的生长、发育、次级代谢合成及环境适应性，为理解放线菌信号转导系统的整体性、动态性及其在基础生命科学研究和生物技术、医学等领域的潜在应用提供参考。

Abstract:

Actinobacteria are Gram-positive bacteria of major ecological and biotechnological importance, responsible for organic matter turnover in nature and serving as a primary source of antibiotics and other bioactive natural products. Their complex physiological adaptation and life cycles are regulated by sophisticated signal transduction networks. This review examines the metabolism, signaling, and regulatory networks of nucleotide second messengers including cyclic diadenosine monophosphate (c-di-AMP), cyclic di-guanosine monophosphate (c-di-GMP), adenosine monophosphate (cAMP), and (p)ppGpp in the morphologically complex Streptomyces with rich secondary metabolites and pathogenic Mycobacterium with host adaptation. We discuss how these second messengers interact with other signaling systems, such as two-component systems, quorum sensing, and protein acylation, to integrate environmental and developmental cues. This coordination regulates the growth, development, secondary metabolite biosynthesis, and environmental adaptation of actinobacteria. By synthesizing current knowledge, this review provides reference for understanding the integrity and dynamics of the signal transduction system of actinobacteria, as well as their potential applications in the basic research of life sciences and in the fields of biotechnology and medicine.