Efophylins A and B, Two C2-Asymmetric Macrodiolide Immunosuppressants from Streptomyces malaysiensis

  • J Nat Prod. 2021 May 28;84(5):1579-1586. doi: 10.1021/acs.jnatprod.1c00118.
Jing Xu  1  2 ,  Xuexia Zhang  1 ,  Fanglu Huang  2 ,  Gang Li  1 ,  Peter F Leadlay  2
Affiliations
  • 1. School of Chemical Engineering and Technology, Hainan University, Haikou 570228, People's Republic of China.
  • 2. Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom.
PMID: 33973788 DOI: 10.1021/acs.jnatprod.1c00118
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.