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Chemoproteomics of microbiota-derived indole metabolites in mammalian cells

ABSTRACT: The microbiota generates diverse metabolites to modulate host physiology and disease, but their protein targets and mechanisms of action have not been fully elucidated. To address this challenge, we focused on microbiota-derived indole metabolites and develop photoaffinity chemical probes for proteomic studies. We identified many potential indoleinteracting proteins, including metabolic enzymes, transporters, immune sensors, and Gprotein coupled receptors. Notably, we discovered aromatic monoamines can activate - arrestin recruitment by the orphan receptor GPRC5A. Metabolomic and functional profiling of microbiota species revealed specific aromatic amino acid decarboxylaseexpressing bacteria producing monoamine agonists for GPRC5A. Structure-activity relationship studies of synthetic aromatic monoamines identified 7-fluorotryptamine as a more potent activator of -arrestin recruitment by GPRC5A. Our results highlight the utility of chemoproteomics to identify novel microbiota metabolite-interacting proteins and discover potential microbiota-derived small molecule agonists for orphan receptors.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Lung Cancer,Colon Cancer

SUBMITTER: Xiaohui Zhao

LAB HEAD: Howard C. Hang

PROVIDER: PXD040163 | Pride | 2023-05-31

REPOSITORIES: Pride

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			Action	DRS
	MS195471QEHF.txt	Txt
	MS195471QEHF_Xiaohui_hang_XZ_DMSO_1.raw	Raw
	MS195471QEHF_Xiaohui_hang_XZ_DMSO_2.raw	Raw
	MS195471QEHF_Xiaohui_hang_XZ_DMSO_3.raw	Raw
	MS195471QEHF_Xiaohui_hang_XZ_DMSO_4.raw	Raw

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Chemoproteomics of microbiota-derived indole metabolites in mammalian cells

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