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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.


Jing Xu, Xuexia Zhang, Fanglu Huang, Gang Li, Peter F Leadlay. Efophylins A and B, Two C2-Asymmetric Macrodiolide Immunosuppressants from Streptomyces malaysiensis. Journal of natural products. 2021 May 28;84(5):1579-1586

PMID: 33973788

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