Reference - Detail
| RRC ID | 75218 |
|---|---|
| Author | Kudo Y, Konoki K, Yotsu-Yamashita M. |
| Title | Mass spectrometry-guided discovery of new analogs of bicyclic phosphotriester salinipostin and evaluation of their monoacylglycerol lipase inhibitory activity. |
| Journal | Biosci Biotechnol Biochem |
| Abstract |
Natural products containing the highly unusual phosphotriester ring are known to be potent serine hydrolase inhibitors. The long-chain bicyclic enol-phosphotriester salinipostins (SPTs) from the marine actinomycete Salinispora have been identified as selective antimalarial agents. A potential regulatory function has been suggested for phosphotriesters based on their structural relationship with actinomycete signaling molecules and the prevalence of spt-like biosynthetic gene clusters across actinomycetes. In this study, we established a mass spectrometry-guided screening method for phosphotriesters focusing on their characteristic fragment ions. Applying this screening method to the SPT producer Salinispora tropica CNB-440, new SPT analogs (4-6) were discovered and their structures were elucidated by spectroscopic analyses. Previously known and herein-identified SPT analogs inhibited the activity of human monoacylglycerol lipase (MAGL), a key serine hydrolase in the endocannabinoid system, in the nanomolar range. Our method could be applied to the screening of phosphotriesters, potential serine hydrolase inhibitors and signaling molecules. |
| Volume | 86(10) |
| Pages | 1333-1342 |
| Published | 2022-9-23 |
| DOI | 10.1093/bbb/zbac131 |
| PII | 6653519 |
| PMID | 35918181 |
| MeSH | Actinobacteria* Antimalarials* Biological Products* Endocannabinoids Enzyme Inhibitors / chemistry Enzyme Inhibitors / pharmacology Humans Mass Spectrometry Monoacylglycerol Lipases / chemistry Monoacylglycerol Lipases / genetics Serine |
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| Total number of mentions | 7 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| General Microbes | JCM 13857 |