美国普林斯顿大学Mohamed S. Donia团队的研究开发出了在拟杆菌门中发现一种广泛存在的化学信号通路。该项研究成果发表在2025年8月20日出版的《自然》上。

在这里，研究小组鉴定并表征了N-酰基环赖氨酸（ACL）系统——一种在拟杆菌门（原拟杆菌门）中特有且广泛存在的细胞密度依赖的化学信号系统——并表明它调节编码多种分泌分子的共定位操纵子的表达。利用遗传和生化分析，结合关键生物合成酶AclA的结构研究，课题组人员阐明了各种ACLs的分子结构及其完整的生物合成途径，包括l-赖氨酸酰化和ATP依赖性环化。

此外，小组发现分泌的ACL被一个专门的转录因子AclR感知，导致相关操纵子的表达和ACL生物合成的自动诱导。

此外，研究人员发现不同的拟杆菌菌株产生结构不同的ACL，并编码具有不同配体特异性的转录因子。最后，研究组发现ACL回路在人类肠道和口腔微生物组样本中广泛分布和转录，有明确的证据表明在宿主定植条件下调节相关操作子的积极作用。了解ACL系统在不同环境下的功能有可能揭示拟杆菌门的生物学、生态学和化学细节，以及该门成员如何与环境和宿主相互作用。

据介绍，在表征细菌分泌的生物活性分子方面已经取得了相当大的进展，但控制其产生的调节元件仍在很大程度上缺乏研究。

附：英文原文

Title: Discovery of a widespread chemical signalling pathway in the Bacteroidota

Author: Linares-Otoya, Luis, Shirkey, Jaden D., Chhetri, Bhuwan Khatri, Mira, Amira, Biswas, Abhishek, Neff, Samuel L., Linares-Otoya, Maria V., Chen, Ye, Campos-Florian, Julio V., Ganoza-Yupanqui, Mayar L., Jeffrey, Philip D., Hughson, Frederick M., Donia, Mohamed S.

Issue&Volume: 2025-08-20

Abstract: Considerable advances have been made in characterizing bioactive molecules secreted by bacteria, yet the regulatory elements controlling their production remain largely understudied. Here we identify and characterize the N-acyl-cyclolysine (ACL) system—a cell-density-dependent chemical signalling system specific to and widespread in the phylum Bacteroidota (formerly Bacteroidetes)—and show that it regulates the expression of co-localized operons encoding diverse secreted molecules. Using genetic and biochemical analyses, combined with structural studies of a key biosynthetic enzyme, AclA, we elucidate the molecular structure of various ACLs and their complete biosynthetic pathway involving l-lysine acylation and ATP-dependent cyclization. Furthermore, we find that secreted ACLs are sensed by a dedicated transcription factor, AclR, resulting in the expression of associated operons and the autoinduction of ACL biosynthesis. Moreover, we show that different Bacteroidota strains produce structurally diverse ACLs and encode transcription factors with varying ligand specificities. Finally, we find that the acl circuit is widely distributed and transcribed in human gut and oral microbiome samples, with clear evidence for an active role in regulating associated operons under host colonization conditions. Understanding the function of the ACL system in different contexts has the potential to reveal details about the biology, ecology and chemistry of the Bacteroidota and how members of this phylum interact with their environments and hosts.

DOI: 10.1038/s41586-025-09418-9

Source: https://www.nature.com/articles/s41586-025-09418-9