An Ugi-like Biosynthetic Pathway Encodes Bombesin Receptor Subtype-3 Agonists
Joonseok Oh1,2, Nam Y Kim1,2, Haiwei Chen3
1Department of Chemistry , Yale University , New Haven , Connecticut 06520 , United States.
Abstract:
Isocyanide functional groups can be found in a variety of natural products. Rhabduscin is one such isocyanide-functionalized immunosuppressant produced in Xenorhabdus and Photorhabdus gammaproteobacterial pathogens, and deletion of its biosynthetic gene cluster inhibits virulence in an invertebrate animal infection model. Here, we characterized the first "opine-glycopeptide" class of natural products termed rhabdoplanins, and strikingly, these molecules are spontaneously produced from rhabduscin via an unprecedented multicomponent "Ugi-like" reaction sequence in nature. The rhabdoplanins also represent new lead G protein-coupled receptor (GPCR) agonists, stimulating the bombesin receptor subtype-3 (BB3) GPCR.
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