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Supporting data for "EXPLORING THE ROLE OF SIGNALING SECONDARY METABOLITES IN BACTERIAL COMMUNICATIONS".

dataset
posted on 2024-06-13, 02:43 authored by Peiyan CaiPeiyan Cai

Throughout their lifespan, bacteria generate diverse natural products postulated to serve as chemical signal mediators and defensive weaponry. However, although enormous natural products have been identified, elucidating their ecological functions, such as antibacterial, antifungal, and quorum sensing (QS) induction properties, remains limited.

In this study, the focus lies on the exploration of novel molecules that function as QS autoinducers or QS inhibitors. Chapter 1 comprehensively reviews the latest advancements in QS autoinducers and inhibitors. Several major families of QS autoinducers are discussed, including N-acyl-homoserine lactones (AHL), autoinducer-2 (AI-2), RRNPP peptides, autoinducing peptides (AIP), and N-heterocycles. Additionally, the principles, examples, and screening models of QS inhibitors are introduced.

Following the review, Chapter 2 delves deeper into the study of N-heterocycles due to their potential to function as both QS autoinducers and QS inhibitors. Given the biosynthetic diversity of N-heterocycles, their corresponding biosynthetic enzymes are examined, with the enzyme family CAR being selected for its untapped biosynthetic potential and prevalence. Through natural product discovery, it was initially determined that CAR-encoded N-heterocycles from Bacillota act as QS inhibitors rather than QS autoinducers. Further enzyme characterization and in vitro product reconstruction revealed that a single CAR enzyme can produce hundreds of N-heterocycles, with a series of pyrazine molecules being identified as QS inhibitors. Considering the widespread occurrence of N-heterocycles, particularly pyrazine molecules, this study provides novel insights into the ecological functions of these ubiquitous molecules.

Chapter 3 details the identification of a novel group of AIPs, which belong to QS autoinducers, derived from the Paenibacillus genus. The discovery of Pp-AIPs was led by a bioactivity-guided search, which provided an opportunity to uncover AIPs with unique biosynthetic features and structures compared to previously known examples. Notably, these AIPs represent the first instance of regulating secondary metabolite production. Consequently, they offer a novel mode of communication with host plants, as the AIPs may assist Paenibacillus in shaping the root microbiome. This study broadens the diversity of AIPs and emphasizes their ecological significance in intricate environmental contexts.

In summary, this study establishes novel links between natural products and QS processes. The findings hold significant potential for guiding and inspiring future research in this area.

Funding

Big Data genomics-Guided Discovery Of New Peptide Antibiotics Against Antibiotic-Resistant Superbugs.

University Grants Committee

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Genome mining-guided and synthetic biology-enabled discovery of ribosomal peptide antibiotics

University Grants Committee

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Genome mining, biosynthesis, and engineering of aminovinyl cysteine-containing peptides for antibiotic discovery

University Grants Committee

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