缺乏C-5脱饱和酶Erg3的酵母对抗炎三萜类皂苷藤黄素具有耐受性。
Yeast lacking the sterol C-5 desaturase Erg3 are tolerant to the anti-inflammatory triterpenoid saponin escin.
发表日期:2023 Aug 21
作者:
Emily J Johnston, Jess Tallis, Edward Cunningham-Oakes, Tessa Moses, Simon J Moore, Sarah Hosking, Susan J Rosser
来源:
ARTHRITIS RESEARCH & THERAPY
摘要:
艾斯金(escin)是从干燥的七叶树果实中提取出的一种混合物,其中含有30多种糖苷化三萜(皂苷)结构。艾斯金目前被用作抗炎药物,并在关节炎和癌症治疗中具有潜在应用。通过工程化的酵母,可以实现工业规模生产艾斯金的特定生物活性成分,然而许多皂苷已被证明对酵母具有毒性。在这里,我们报告了Saccharomyces cerevisiae株突变的C-5脱氢酶基因ERG3缺失,显示出对艾斯金处理的明显增强耐受性。转录组分析以及将艾斯金与固醇预混合的实验支持了艾斯金与麦角固醇直接相互作用的假设,但对于erg3Δ中存在的变异固醇的作用则不强烈。多样化的皂苷具有商业价值,这项研究突出了筛选脂质组突变体以确定合适的宿主用于工程化生产皂苷的价值。© 2023. Springer Nature Limited.
Escin is a mixture of over 30 glycosylated triterpenoid (saponin) structures, extracted from the dried fruit of horse chestnuts. Escin is currently used as an anti-inflammatory, and has potential applications in the treatment of arthritis and cancer. Engineered yeast would enable production of specific bioactive components of escin at industrial scale, however many saponins have been shown to be toxic to yeast. Here we report that a Saccharomyces cerevisiae strain specifically lacking the sterol C-5 desaturase gene ERG3, exhibits striking enhanced tolerance to escin treatment. Transcriptome analyses, as well as pre-mixing of escin with sterols, support the hypothesis that escin interacts directly with ergosterol, but not as strongly with the altered sterols present in erg3Δ. A diverse range of saponins are of commercial interest, and this research highlights the value of screening lipidome mutants to identify appropriate hosts for engineering the industrial production of saponins.© 2023. Springer Nature Limited.