Activation of the NLRP3 Inflammasome by Hyaboron, a New Asymmetric Boron-Containing Macrodiolide from the Myxobacterium Hyalangium minutum

Surup, Frank; Chauhan, Dhruv; Niggemann, Jutta; Bartok, Eva; Herrmann, Jennifer; Keck, Matthias; Zander, Wiebke; Stadler, Marc; Hornung, Veit und Müller, Rolf (2018): Activation of the NLRP3 Inflammasome by Hyaboron, a New Asymmetric Boron-Containing Macrodiolide from the Myxobacterium Hyalangium minutum. In: ACS Chemical Biology, Bd. 13, Nr. 10: S. 2981-2988

Abstract

A Natural Compound Library containing myxobacterial secondary metabolites was screened in murine macrophages for novel activators of IL-1/beta maturation and secretion. The most potent of three hits in total was a so far undescribed metabolite, which was identified from the myxobacterium Hyalangium minutum strain Hym3. While the planar structure of 1 was elucidated by high resolution mass spectrometry and NMR data yielding an asymmetric boron containing a macrodiolide core structure, its relative stereochemistry of all 20 stereocenters of the 42-membered ring was assigned by rotating frame Overhause effect spectroscopy correlations, H-1,H-1, and H-1,C-13 coupling constants, and by comparison of C-13 chemical shifts to those of the structurally related metabolites tartrolon B-D. The absolute stereochemistry was subsequently assigned by Mosher's and Marfey's methods. Further functional studies revealed that hyaboron and other boronated natural compounds resulted in NLRP3 inflammasome dependent IL-1/beta maturation, which is most likely due to their ability to act as potassium ionophores. Moreover, besides its inflammasome-stimulatory activity in human and mouse cells, hyaboron (1) showed additional diverse biological activities, including antibacterial and antiparasitic effects.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department Biochemie
• Fakultätsübergreifende Einrichtungen: Center for Integrated Protein Science Munich (CIPSM)
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 1554-8929
• Sprache: Englisch