埃福菲林A和B，两种来自于……的不对称大环二酯类免疫抑制剂

Efophylins A and B, Two -Asymmetric Macrodiolide Immunosuppressants from .

作者信息

Xu Jing, Zhang Xuexia, Huang Fanglu, Li Gang, Leadlay Peter F

机构信息

School of Chemical Engineering and Technology, Hainan University, Haikou 570228, People's Republic of China.

Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom.

出版信息

J Nat Prod. 2021 May 28;84(5):1579-1586. doi: 10.1021/acs.jnatprod.1c00118. Epub 2021 May 11.

DOI:10.1021/acs.jnatprod.1c00118

PMID:33973788

Abstract

Genomics-inspired isolation led to the identification of two new natural congeneric -asymmetric macrodiolide immunosuppressants, named efophylins A () and B (), from DSM 4137. Their structures were elucidated by spectroscopic and computational methods and were in agreement with biosynthetic predictions from the efophylin gene cluster. Compound exhibited potent immunosuppressive activity and demonstrated to inhibit the activation of the NFAT and block NFAT dephosphorylation . The immunosuppressive activity of compound is possibly at least in part via the CaN/NFAT signaling pathway.

摘要

受基因组学启发的分离方法，使得从DSM 4137中鉴定出两种新的天然同属不对称大环二萜免疫抑制剂，命名为依福林A（）和依福林B（）。通过光谱和计算方法阐明了它们的结构，这些结构与依福林基因簇的生物合成预测结果一致。化合物表现出强大的免疫抑制活性，并证明能抑制NFAT的激活并阻断NFAT去磷酸化。化合物的免疫抑制活性可能至少部分是通过CaN/NFAT信号通路实现的。