Department of Chemistry, University of Prince Edward Island, Charlottetown, PE C1A 4P3, Canada.
Nautilus Biosciences Croda, Regis and Joan Duffy Research Centre, 550 University Avenue, Charlottetown, PE C1A 4P3, Canada.
Mar Drugs. 2019 Jul 24;17(8):435. doi: 10.3390/md17080435.
Advances in whole-genome sequencing of many fungal species has revealed the presence of numerous "silent" biosynthetic genes, highlighting their potential to produce a wide variety of natural products. These silent biosynthetic genes are regulated in part by their highly condensed chromatin structure, which can be modified to allow transcription in response to external stimuli. In this study, was subjected to both epigenetic modification and osmotic stress to enhance the production of new natural products. This "cooperative induction" strategy led to the isolation and characterization of two new polyketides from a fermentation of treated with suberoylanilide hydroxamic acid and sodium chloride. The metabolic profiles of the control and treated samples were assessed using ultra-high performance liquid chromatography high-resolution electrospray ionization mass spectrometry (UHPLC-HRESIMS) metabolomic analysis, highlighting the upregulation of two new polyketides, primarolides A and B. These compounds were purified using reversed-phase flash chromatography followed by high-performance liquid chromatography, and their planar structures were established using NMR spectroscopy.
许多真菌物种的全基因组测序的进展揭示了大量“沉默”生物合成基因的存在，这凸显了它们产生各种天然产物的潜力。这些沉默的生物合成基因部分受其高度浓缩的染色质结构调控，这种结构可以被修饰以允许转录响应外部刺激。在这项研究中，对 进行了表观遗传修饰和渗透压胁迫处理，以增强新天然产物的产生。这种“协同诱导”策略导致了从用琥珀酰亚胺基羟肟酸和氯化钠处理的 发酵中分离和表征两种新的聚酮化合物。使用超高效液相色谱高分辨率电喷雾电离质谱（UHPLC-HRESIMS）代谢组学分析评估了对照和处理样品的代谢谱，突出了两种新的聚酮化合物，即 primarolide A 和 B 的上调。这些化合物使用反相快速色谱法和高效液相色谱法进行纯化，并通过核磁共振波谱法确定了它们的平面结构。
