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

J Nat Prod. 2024 Jul 26;87(7):1735-1745. doi: 10.1021/acs.jnatprod.4c00225.

Ling Shen ¹, Yanyan Wang ¹, Chengxin Liu ¹, Wula Alateng ², Yuxin Wang ¹, Axel Zeeck ³, Weiguang Wang ⁴, Peng Zhang ¹, Yanhong Wei ², Xiaofeng Cai ¹ ⁵

Affiliations

1 Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
2 Sino-German Biomedical Center, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, People's Republic of China.
3 Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Göttingen 37073, Germany.
4 Key Laboratory of Chemistry in Ethnic Medicinal Resources, Ministry of Education, Yunnan Minzu University, Kunming 650031, People's Republic of China.
5 State Key Laboratory of Dao-di Herbs, Beijing 100700, People's Republic of China.

PMID: 38976838 DOI: 10.1021/acs.jnatprod.4c00225

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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