Ocean College, Zhejiang University, Zhoushan 321000, China.
College of Pharmaceutical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, China.
Anal Chem. 2024 Apr 9;96(14):5399-5406. doi: 10.1021/acs.analchem.3c05057. Epub 2024 Mar 24.
Natural product discovery is hindered by the lack of tools that integrate untargeted nuclear magnetic resonance and mass spectrometry data on a library scale. This article describes the first application of the innovative NMR/MS-based machine learning tool, the "Structure-Oriented Fractions Screening Platform (SFSP)", enabling functional-group-guided fractionation and accelerating the discovery and characterization of undescribed natural products. The concept was applied to the extract of a marine fungus known to be a prolific producer of diverse natural products. With the assistance of SFSP, we isolated 24 flavipidin derivatives and five phenalenone analogues from sp. GE2-6, revealing 27 undescribed compounds. Compounds - were proposed as isomeric derivatives featuring a 5/6-ring fusion, formed by the dimerization of flavipidin E (). Compounds and were envisaged as isomeric derivatives with a 6/5/6-ring fusion, generated through the degradation of two flavipidin E molecules. Furthermore, flavipidin A () and asperphenalenone E () exhibited potent anti-influenza (PR8) activities, with IC values of 21.9 ± 0.2 and 12.9 ± 0.1 μM, respectively. Meanwhile, asperphenalenone () and asperphenalenone P () treatments exhibited significant inhibition of HIV pseudovirus infection in 293FT cells, boasting IC values of 6.1 ± 0.9 and 4.6 ± 1.1 μM, respectively. Overall, SFSP streamlines natural product isolation through NMR and MS data integration, as showcased by the discovery of numerous undescribed flavipidins and phenalenones based on NMR olefinic signals and low-field hydroxy signals.
天然产物的发现受到缺乏工具的限制，这些工具无法在库规模上整合非靶向核磁共振和质谱数据。本文介绍了创新的基于 NMR/MS 的机器学习工具“结构导向馏分筛选平台 (SFSP)”的首次应用，该工具能够实现基于功能基团的馏分分离，加速未知天然产物的发现和表征。该概念应用于一种已知是多种天然产物丰富生产者的海洋真菌提取物。在 SFSP 的协助下，我们从 sp. GE2-6 中分离出 24 种 flavipidin 衍生物和 5 种 phenalenone 类似物，揭示了 27 种未描述的化合物。化合物 - 被提出为具有 5/6-环融合的同系物衍生物，由 flavipidin E () 的二聚体形成。化合物 和 被设想为具有 6/5/6-环融合的同系物衍生物，通过两个 flavipidin E 分子的降解产生。此外，flavipidin A () 和 asperphenalenone E () 表现出强烈的抗流感（PR8）活性，IC 值分别为 21.9 ± 0.2 和 12.9 ± 0.1 μM。同时，asperphenalenone () 和 asperphenalenone P () 处理对 293FT 细胞中的 HIV 假病毒感染表现出显著的抑制作用，IC 值分别为 6.1 ± 0.9 和 4.6 ± 1.1 μM。总体而言，SFSP 通过 NMR 和 MS 数据集成简化了天然产物的分离，通过基于 NMR 烯烃信号和低场羟基信号发现了许多未描述的 flavipidins 和 phenalenones 来证明这一点。
