Departamento de Biotecnología, Instituto de Agroquímica y Tecnología de Alimentos (IATA), Consejo Superior de Investigaciones Científicas (CSIC), Agustín Escardino 7, E-46980 Paterna, Valencia, Spain.
Genes (Basel). 2020 Jul 15;11(7):795. doi: 10.3390/genes11070795.
Ergosterol is an essential component of fungal cell membranes that determines the fluidity, permeability and activity of membrane-associated proteins. Ergosterol biosynthesis is a complex and highly energy-consuming pathway that involves the participation of many enzymes. Deficiencies in sterol biosynthesis cause pleiotropic defects that limit cellular proliferation and adaptation to stress. Thereby, fungal ergosterol levels are tightly controlled by the bioavailability of particular metabolites (e.g., sterols, oxygen and iron) and environmental conditions. The regulation of ergosterol synthesis is achieved by overlapping mechanisms that include transcriptional expression, feedback inhibition of enzymes and changes in their subcellular localization. In the budding yeast , the sterol regulatory element (SRE)-binding proteins Upc2 and Ecm22, the heme-binding protein Hap1 and the repressor factors Rox1 and Mot3 coordinate ergosterol biosynthesis () gene expression. Here, we summarize the sterol biosynthesis, transport and detoxification systems of , as well as its adaptive response to sterol depletion, low oxygen, hyperosmotic stress and iron deficiency. Because of the large number of genes and the crosstalk between different environmental signals and pathways, many aspects of ergosterol regulation are still unknown. The study of sterol metabolism and its regulation is highly relevant due to its wide applications in antifungal treatments, as well as in food and pharmaceutical industries.
麦角甾醇是真菌细胞膜的重要组成部分，决定了膜相关蛋白的流动性、通透性和活性。麦角甾醇生物合成是一个复杂且高度耗能的途径，涉及许多酶的参与。甾醇生物合成的缺陷会导致多效缺陷，限制细胞增殖和适应应激。因此，真菌麦角甾醇水平受到特定代谢物（如甾醇、氧气和铁）生物利用度和环境条件的严格控制。麦角甾醇合成的调节是通过重叠的机制实现的，包括转录表达、酶的反馈抑制以及它们亚细胞定位的变化。在出芽酵母中，甾醇调节元件（SRE）结合蛋白 Upc2 和 Ecm22、血红素结合蛋白 Hap1 以及阻遏因子 Rox1 和 Mot3 协调麦角甾醇生物合成（）基因表达。在这里，我们总结了 的麦角甾醇生物合成、运输和解毒系统，以及它对麦角甾醇耗竭、低氧、高渗应激和缺铁的适应性反应。由于大量的 基因和不同环境信号和途径之间的相互作用，麦角甾醇调节的许多方面仍然未知。由于其在抗真菌治疗以及食品和制药工业中的广泛应用，麦角甾醇代谢及其调节的研究具有重要意义。
