{"database":"GNPS","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://massive-ftp.ucsd.edu/v03/MSV000086958/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":0,"searchCount":0},"additional":{"omics_type":["Metabolomics"],"submitter":["Koenig / Cruesemann"],"instrument_platform":["microTOF LC"],"species":["Chromobacterium Vaccinii (ncbitaxon:1108595)","Ardisia Crenata (ncbitaxon:13345)"],"full_dataset_link":["https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=1e5d230149ef43d9aad5b069c7339556"],"submitter_email":["wiebke.hanke@freenet.de"],"submitter_affiliation":["University of Bonn"],"sample_protocol":[""],"repository":["GNPS"],"file_size":["65"],"ptm_modification":["MS:1002864 - No post-translational-modifications are included in the identified peptides of this dataset"],"data_protocol":[""],"citation_count":["0"],"additional_accession":[]},"is_claimable":false,"name":"GNPS-FeaturebasedMolecularNetworkingFRDerivativesJNP","description":"Both, the soil bacterium Chromobacterium vaccinii and the bacterial endosymbiont Candidatus Burkholderia crenata of the plant Ardisia crenata are producers of FR900359 (FR). This cyclic depsipeptide is a potent and selective Gq protein inhibitor and used extensively to investigate the intracellular signaling of G protein coupled receptors (GPCRs). In this study, the metabolomes of both FR producers were investigated and compared using feature-based molecular networking (FBMN). As a result, 30 to date unknown FR derivatives were identified, one third of which being unique to C. vaccinii. Guided by MS, a novel FR derivative, FR-6 (compound 1), was isolated, and its structure unambiguously established. In a whole cell biosensing assay based on detection of dynamic mass redistribution (DMR) as readout for Gq inhibition, FR-6 suppressed Gq signaling with micromolar potency (pIC50=5.56). This functional activity was confirmed in radioligand binding assays (pKi=7.50). This work demonstrates the power of molecular networking, guiding the way to a novel Gq inhibiting FR derivative, and underlining the potency of FR as Gq inhibitor.","dates":{"publication":"Fri Feb 26 02:33:00 GMT 2021"},"accession":"MSV000086958","cross_references":{}}