Efophylins A and B, Two <i>C</i><sub>2</sub>-Asymmetric Macrodiolide Immunosuppressants from <i>Streptomyces malaysiensis</i>
Jing Xu, Xuexia Zhang, Fanglu Huang, Gang Li, Peter F. Leadlay
Abstract
Genomics-inspired isolation led to the identification of two new natural congeneric C2-asymmetric macrodiolide immunosuppressants, named efophylins A (1) and B (2), from Streptomyces malaysiensis DSM 4137. Their structures were elucidated by spectroscopic and computational methods and were in agreement with biosynthetic predictions from the efophylin gene cluster. Compound 2 exhibited potent immunosuppressive activity and demonstrated to inhibit the activation of the NFAT and block NFAT dephosphorylation in vitro. The immunosuppressive activity of compound 2 is possibly at least in part via the CaN/NFAT signaling pathway.
Topics & Concepts
NFATStereochemistryStreptomycetaceaeBiologyStreptomycesChemistryBiochemistryGeneGeneticsActinomycetalesTranscription factorBacteriaMicrobial Natural Products and BiosynthesisMarine Sponges and Natural ProductsTraditional and Medicinal Uses of Annonaceae