Discovery of Meroterpenoids with Antifungal Activity from Deep-Sea-Derived Fungus Acremonium sclerotigenum LW14

作者：Ruiyun Huo, Minhui Ji, Guangrong Zi, Shuangshuang Feng, Lei Cai, Ling Liu · 发表于：Journal of Natural Products · 年份：2025 · DOI：10.1021/acs.jnatprod.5c01286 · 被引用次数：2 · 研究领域：Microbial Natural Products and Biosynthesis、Marine Sponges and Natural Products、Bryophyte Studies and Records

Thirteen previously unreported ascochlorin-type meroterpenoids, acrocholrins A–M ( 1 – 13 ), together with seven known analogues ( 14 – 20 ) were characterized from the deep-sea-derived fungus Acremonium sclerotigenum LW14 guided by LC-MS/MS-based molecular networking. Their structures and absolute configurations were determined unambiguously by spectroscopic analysis, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction experiments. Compounds 1 / 3, 2 / 14, 6 / 7, 8 / 17, and 15 / 16 are diastereomers isomerized at C-10. Additionally, compounds 5, 11, 12, and 13 represent rare ascochlorin analogues featuring an uncommon 19 S configuration in the cyclohexanone ring. Compounds 9, 11, and 19 exhibited antifungal activity against Cryptococcus gattii 3271G1 with the same minimum inhibitory concentration (MIC) of 4 μg/mL. Preliminary mechanistic studies showed that compound 9 exhibited its anti- C. gattii activity by inhibiting capsule formation and increasing cell membrane permeability.