Hunan Institute of Microbiology, Changsha 410009, China.
State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Helmholtz International Lab for Anti-infectives, Shandong University-Helmholtz Institute of Biotechnology, Shandong University, Qingdao 266237, China.
Molecules. 2021 Nov 20;26(22):7020. doi: 10.3390/molecules26227020.
Phytopathogenic fungi infect crops, presenting a worldwide threat to agriculture. Polyene macrolides are one of the most effective antifungal agents applied in human therapy and crop protection. In this study, we found a cryptic polyene biosynthetic gene cluster in by genome mining. Then, this gene cluster was activated via varying fermentation conditions, leading to the discovery of new polyene actinospene (), which was subsequently isolated and its structure determined through spectroscopic techniques including UV, HR-MS, and NMR. The absolute configuration was confirmed by comparing the calculated and experimental electronic circular dichroism (ECD) spectra. Unlike known polyene macrolides, actinospene () demonstrated more versatile post-assembling decorations including two epoxide groups and an unusual isobutenyl side chain. In bioassays, actinospene () showed a broad spectrum of antifungal activity against several plant fungal pathogens as well as pathogenic yeasts with minimum inhibitory concentrations ranging between 2 and 10 μg/mL.
植物病原真菌侵染作物，对农业造成全球性威胁。多烯大环内酯类化合物是应用于人类治疗和作物保护的最有效的抗真菌剂之一。在本研究中，我们通过基因组挖掘在 中发现了一个隐藏的多烯生物合成基因簇。然后，通过改变发酵条件激活该基因簇，发现了新的多烯放线孢烯（），随后通过包括紫外、高分辨质谱和 NMR 在内的光谱技术分离并确定其结构。通过比较计算和实验电子圆二色谱（ECD）谱来确定绝对构型。与已知的多烯大环内酯不同，放线孢烯（）表现出更具多功能性的后组装修饰，包括两个环氧化物基团和一个不寻常的异丁烯基侧链。在生物测定中，放线孢烯（）对几种植物病原真菌和致病性酵母表现出广谱的抗真菌活性，最低抑菌浓度范围在 2 至 10 μg/mL 之间。
