Wang Yu, Wu Tao, Fan Xuqian, Ruan Haihua, Fan Feiyu, Zhang Xueli
School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China.
Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.
Sheng Wu Gong Cheng Xue Bao. 2023 Aug 25;39(8):3204-3218. doi: 10.13345/j.cjb.230042.
Sterols are a class of cyclopentano-perhydrophenanthrene derivatives widely present in living organisms. Sterols are important components of cell membranes. In addition, they also have important physiological and pharmacological activities. With the development of synthetic biology and metabolic engineering technology, yeast cells are increasingly used for the heterologous synthesis of sterols in recent years. Nevertheless, since sterols are hydrophobic macromolecules, they tend to accumulate in the membrane fraction of yeast cells and consequently trigger cytotoxicity, which hampers the further improvement of sterols yield. Therefore, revealing the mechanism of sterol transport in yeast, especially understanding the working principle of sterol transporters, is vital for designing strategies to relieve the toxicity of sterol accumulation and increasing sterol yield in yeast cell factories. In yeast, sterols are mainly transported through protein-mediated non-vesicular transport mechanisms. This review summarizes five types of sterol transport-related proteins that have been reported in yeast, namely OSBP/ORPs family proteins, LAM family proteins, ABC transport family proteins, CAP superfamily proteins, and NPC-like sterol transport proteins. These transporters play important roles in intracellular sterol gradient distribution and homeostasis maintenance. In addition, we also review the current status of practical applications of sterol transport proteins in yeast cell factories.
甾醇是一类广泛存在于生物体中的环戊烷多氢菲衍生物。甾醇是细胞膜的重要组成成分。此外，它们还具有重要的生理和药理活性。随着合成生物学和代谢工程技术的发展，近年来酵母细胞越来越多地用于甾醇的异源合成。然而，由于甾醇是疏水性大分子，它们倾向于在酵母细胞的膜部分积累，从而引发细胞毒性，这阻碍了甾醇产量的进一步提高。因此，揭示酵母中甾醇转运的机制，尤其是了解甾醇转运蛋白的工作原理，对于设计减轻甾醇积累毒性的策略和提高酵母细胞工厂中甾醇产量至关重要。在酵母中，甾醇主要通过蛋白质介导的非囊泡转运机制进行转运。本综述总结了酵母中已报道的五类与甾醇转运相关的蛋白质，即OSBP/ORPs家族蛋白、LAM家族蛋白、ABC转运家族蛋白、CAP超家族蛋白和NPC样甾醇转运蛋白。这些转运蛋白在细胞内甾醇梯度分布和稳态维持中发挥着重要作用。此外，我们还综述了甾醇转运蛋白在酵母细胞工厂实际应用的现状。
