小柯机器人

美国耶鲁大学Noah W. Palm等研究人员合作发现，高度复用的生物活性筛选揭示人类和微生物群的代谢组-GPCR组的相互作用。2023年6月14日，《细胞》杂志在线发表了这项成果。

研究人员开发了一种名为PRESTO-Salsa的高度复用筛选技术，能够在96孔板的一个孔中同时评估几乎所有的常规G-蛋白偶联受体（GPCR）（>300个受体）。利用PRESTO-Salsa，研究人员针对GPCR组筛选了1041种人类相关的代谢物，并发现了以前未报告的内源性、外源性和微生物GPCR激动剂。接下来，研究人员利用PRESTO-Salsa生成了来自多个身体部位的435个人类微生物组菌株的微生物-GPCR相互作用图谱，并揭示了跨组织GPCR参与的保守模式以及牙龈卟啉单胞菌蛋白酶ginipain K对CD97/ADGRE5的激活。

据了解，人体含有数以千计的来自哺乳动物细胞、微生物群、食物和医疗药物的代谢物。许多生物活性代谢物通过GPCR的参与而发挥作用；然而，技术上的限制制约了目前对代谢物-GPCR相互作用的探索。

附：英文原文

Title: Highly multiplexed bioactivity screening reveals human and microbiota metabolome-GPCRome interactions

Author: Haiwei Chen, Connor E. Rosen, Jaime A. González-Hernández, Deguang Song, Jan Potempa, Aaron M. Ring, Noah W. Palm

Issue&Volume: 2023-06-14

Abstract: The human body contains thousands of metabolites derived from mammalian cells, themicrobiota, food, and medical drugs. Many bioactive metabolites act through the engagementof G-protein-coupled receptors (GPCRs); however, technological limitations constraincurrent explorations of metabolite-GPCR interactions. Here, we developed a highlymultiplexed screening technology called PRESTO-Salsa that enables simultaneous assessmentof nearly all conventional GPCRs (>300 receptors) in a single well of a 96-well plate.Using PRESTO-Salsa, we screened 1,041 human-associated metabolites against the GPCRomeand uncovered previously unreported endogenous, exogenous, and microbial GPCR agonists.Next, we leveraged PRESTO-Salsa to generate an atlas of microbiome-GPCR interactionsacross 435 human microbiome strains from multiple body sites, revealing conservedpatterns of cross-tissue GPCR engagement and activation of CD97/ADGRE5 by the Porphyromonas gingivalis protease gingipain K. These studies thus establish a highly multiplexed bioactivityscreening technology and expose a diverse landscape of human, diet, drug, and microbiotametabolome-GPCRome interactions.

DOI: 10.1016/j.cell.2023.05.024

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00543-3