Exploration of Chemical Diversity in Intercellular Quorum Sensing Signalling Systems in Prokaryotes

Christopher Jonkergouw, Pihla Savola, Ekaterina Osmekhina, Joeri van Strien, Piotr Batys, Markus B. Linder*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

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Abstract

Quorum sensing (QS) serves as a vital means of intercellular signalling in a variety of prokaryotes, which enables single cells to act in multicellular configurations. The potential to control community-wide responses has also sparked numerous recent biotechnological innovations. However, our capacity to utilize intercellular communication is hindered due to a scarcity of complementary signalling systems and a restricted comprehension of interconnections between these systems caused by variations in their dynamic range. In this study, we utilize uniform manifold approximation and projection and extended-connectivity fingerprints to explore the available chemical space of QS signalling molecules. We investigate and experimentally characterize a set of closely related QS signalling ligands, consisting of N-acyl homoserine lactones and the aryl homoserine lactone p-coumaroyl, as well as a set of more widely diverging QS ligands, consisting of photopyrones, dialkylresorcinols, 3,5-dimethylpyrazin-2-ol and autoinducer-2, and define their performance. We report on a set of six signal- and promoter-orthogonal intercellular QS signalling systems, significantly expanding the toolkit for engineering community-wide behaviour. Furthermore, we demonstrate that ligand diversity can serve as a statistically significant tool to predict much more complicated ligand-receptor interactions. This approach highlights the potential of dimensionality reduction to explore chemical diversity in microbial dynamics.

Original languageEnglish
Article numbere202314469
JournalAngewandte Chemie - International Edition
Volume63
Issue number2
Early online date10 Nov 2023
DOIs
Publication statusPublished - 8 Jan 2024
MoE publication typeA1 Journal article-refereed

Keywords

  • Chemical Biology
  • Molecular Dynamics
  • Quorum-Sensing
  • Receptor-Ligand Interactions
  • Structural Fingerprinting

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