Cytochalasans are a large family of well-studied cytotoxic molecules isolated from fungi. Investigation into the organic extract of the marine-derived fungal strain Aspergillus flavipes CNL-338 led to the isolation of seven leucine-containing cytochalasans. Genome mining allowed for the identification of the ffs biosynthetic gene cluster, and genetic inactivation studies verified its involvement in cytochalasan biosynthesis. In addition, comparative analysis of key residues in the binding pocket of core cytochalasan biosynthetic enzymes revealed significant similarities among fungal adenylation domains despite differences in substrate preference. We report the identification of leucine-containing cytochalasans from the marine-derived A. flavipes CNL-338 and the characterization of the ffs biosynthetic cluster as verified by genetic inactivation studies.

细胞松弛素是从真菌中分离出来的经过广泛研究的细胞毒性分子大家族。对海洋来源的真菌菌株黄曲霉CNL-338的有机提取物的研究导致分离出七个含亮氨酸的细胞松弛素。基因组挖掘可以识别ffs生物合成基因簇，而基因灭活研究证实其参与了细胞松弛素的生物合成。另外，对核心细胞松弛素生物合成酶结合口袋中关键残基的比较分析显示，尽管底物偏好不同，真菌腺苷酸化结构域之间也存在显着相似性。我们报告从海洋来源的黄曲霉的含亮氨酸的细胞松弛素的鉴定。CNL-338和ffs生物合成簇的表征已通过基因灭活研究证实。