PDF(Pubmed)
Abstract：
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 Actinokineospora spheciospongiae by genome mining. Then, this gene cluster was activated via varying fermentation conditions, leading to the discovery of new polyene actinospene (1), 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 (1) demonstrated more versatile post-assembling decorations including two epoxide groups and an unusual isobutenyl side chain. In bioassays, actinospene (1) 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.
摘要：
植物病原真菌感染作物，对农业构成全球性威胁。多烯大环内酯是应用于人类治疗和作物保护的最有效的抗真菌剂之一。在这项研究中,通过基因组挖掘，我们发现了一个隐蔽的多烯生物合成基因簇。然后，这个基因簇通过不同的发酵条件被激活，导致发现了新的多烯放线菌（1），随后被分离，并通过包括紫外线在内的光谱技术确定其结构，HR-MS,和NMR。通过比较计算的和实验的电子圆二色性（ECD）光谱来确认绝对构型。与已知的多烯大环内酯不同，放线菌素（1）表现出更多功能的组装后装饰，包括两个环氧基团和一个不寻常的异丁烯基侧链。在生物测定中，放线菌（1）对几种植物真菌病原体和致病性酵母具有广谱的抗真菌活性，最小抑制浓度在2至10μg/mL之间。
