Genome-Driven Discovery of Antiviral Atralabdans A-C from the Soil-Dwelling Streptomyces atratus.

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL Journal of Natural Products Pub Date : 2024-07-26 Epub Date: 2024-07-08 DOI:10.1021/acs.jnatprod.4c00225

Ling Shen, Yanyan Wang, Chengxin Liu, Wula Alateng, Yuxin Wang, Axel Zeeck, Weiguang Wang, Peng Zhang, Yanhong Wei, Xiaofeng Cai

引用次数: 0

Abstract

Heterologous expression of an atr terpenoid gene cluster derived from Streptomyces atratus Gö66 in S. albus J1074 led to the discovery of three novel labdane diterpenoids featuring an unprecedented 6/6/5-fused tricyclic skeleton, designated as atralabdans A-C (1-3), along with a known compound, labdanmycin A. Compounds 1-3 were identified through extensive spectroscopic analysis, including NMR calculations with DP4+ probability analysis, and a comparative assessment of experimental and theoretical electronic circular dichroism (ECD) spectra. A plausible biosynthetic pathway for these compounds was proposed. Compounds 1-3 exhibited inhibitory activity against the human neurotropic coxsackievirus B3 (CVB3); 1 was the most potent, surpassing the positive control ribavirin with a higher therapeutic index.

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基因组驱动从土栖链霉菌中发现抗病毒的 Atralabdans A-C。

通过在 S. albus J1074 中异源表达源自阿特拉普氏链霉菌 Gö66 的阿特拉普氏萜类化合物基因簇，发现了三种新型拉班二萜，它们具有前所未有的 6/6/5 融合三环骨架，与已知化合物拉班霉素 A 一起被命名为阿特拉普氏萜 A-C（1-3）。通过广泛的光谱分析，包括利用 DP4+ 概率分析进行核磁共振计算，以及对实验和理论电子圆二色性（ECD）光谱进行比较评估，确定了 1-3 号化合物。提出了这些化合物的合理生物合成途径。化合物 1-3 对人类神经性柯萨奇病毒 B3（CVB3）具有抑制活性；其中化合物 1 的效力最强，以更高的治疗指数超过了阳性对照利巴韦林。

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来源期刊

Journal of Natural Products 生物-药学

CiteScore

9.10

自引率

5.90%

发文量

294

审稿时长

2.3 months

期刊介绍： The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.