Division of Biochemical Technology, School of Bioresources and Technology, King Mongkut's University of Technology Thonburi (KMUTT), Bangkok, 10150, Thailand.
Division of Fermentation Technology, Faculty of Food Industry, King Mongkut's Institute of Technology Ladkrabang (KMITL), Bangkok, 10520, Thailand.
Sci Rep. 2021 Apr 8;11(1):7779. doi: 10.1038/s41598-021-87342-4.
Repetitive uses of antifungals result in a worldwide crisis of drug resistance; therefore, natural fungicides with minimal side-effects are currently sought after. This study aimed to investigate antifungal property of 19, 20-epoxycytochalasin Q (ECQ), derived from medicinal mushroom Xylaria sp. BCC 1067 of tropical forests. In a model yeast Saccharomyces cerevisiae, ECQ is more toxic in the erg6∆ strain, which has previously been shown to allow higher uptake of many hydrophilic toxins. We selected one pathway to study the effects of ECQ at very high levels on transcription: the ergosterol biosynthesis pathway, which is unlikely to be the primary target of ECQ. Ergosterol serves many functions that cholesterol does in human cells. ECQ's transcriptional effects were correlated with altered sterol and triacylglycerol levels. In the ECQ-treated Δerg6 strain, which presumably takes up far more ECQ than the wild-type strain, there was cell rupture. Increased actin aggregation and lipid droplets assembly were also found in the erg6∆ mutant. Thereby, ECQ is suggested to sensitize yeast cells lacking ERG6 through actin-targeting and consequently but not primarily led to disruption of lipid homeostasis. Investigation of cytochalasins may provide valuable insight with potential biopharmaceutical applications in treatments of fungal infection, cancer or metabolic disorder.
抗真菌药物的反复使用导致了全球范围内的耐药性危机；因此，目前人们正在寻找副作用最小的天然杀菌剂。本研究旨在研究来源于热带森林药用真菌木层孔菌 BCC 1067 的 19, 20-环氧细胞松弛素 Q（ECQ）的抗真菌特性。在模式酵母酿酒酵母中，ECQ 在 erg6∆ 菌株中毒性更大，先前的研究表明，erg6∆ 菌株允许更多的亲水性毒素进入细胞。我们选择了一条途径来研究 ECQ 对转录的非常高的水平的影响：麦角固醇生物合成途径，该途径不太可能是 ECQ 的主要靶标。麦角固醇在人类细胞中具有许多胆固醇的功能。ECQ 的转录效应与固醇和三酰基甘油水平的改变有关。在假定摄取了比野生型菌株更多 ECQ 的 erg6∆ 处理菌株中，细胞破裂。在 erg6∆ 突变体中还发现了肌动蛋白聚集和脂滴组装的增加。因此，ECQ 通过靶向肌动蛋白使缺乏 ERG6 的酵母细胞变得敏感，并且不是主要导致脂质动态平衡的破坏。细胞松弛素的研究可能为真菌感染、癌症或代谢紊乱的治疗提供有价值的见解和潜在的生物制药应用。
