Eating up eATP | Nature Chemical Biology


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Access through your institution Buy or subscribe _Nat. Med_. 27, 1212–1222 (2021) Activated immune cells and commensal bacteria in the mammalian gut release extracellular ATP (eATP), which


activates purinergic receptors that trigger increased production of pro-inflammatory cytokines, activation of effector T cells, and other processes involved in the pathology of inflammatory


bowel disease (IBD). In an effort to develop treatments for IBD, Scott and Gutiérrez-Vázquez et al. engineered a probiotic strain of _Saccharomyces cerevisiae_ that responds to and


intercepts the eATP signal. To construct the probiotic yeast, the authors first used directed evolution on the human purinergic receptor P2Y2 to obtain a variant with increased sensitivity


and selectivity for eATP, then constructed a gene circuit in which activation of P2Y2 induces expression and secretion of the plant eATP-degrading enzyme apyrase. When orally administered in


mouse models of IBD, the engineered yeast mitigated elevated eATP levels, inflammation and intestinal pathology, prevented the formation of fibrotic lesions, and maintained normal levels of


microbiome diversity. The construction of this selective and effective probiotic strain demonstrates the utility of synthetic biology in targeting and treating inflammation-linked diseases


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Chemical Biology https://www.nature.com/nchembio/ Caitlin Deane Authors * Caitlin Deane View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING


AUTHOR Correspondence to Caitlin Deane. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Deane, C. Eating up eATP. _Nat Chem Biol_ 17, 1010 (2021).


https://doi.org/10.1038/s41589-021-00885-5 Download citation * Published: 22 September 2021 * Issue Date: October 2021 * DOI: https://doi.org/10.1038/s41589-021-00885-5 SHARE THIS ARTICLE


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