酵母甾醇转运蛋白研究进展

Sterol transport proteins in yeast: a review

摘要:

甾醇是一类广泛存在于生物体内的环戊烷骈多氢菲衍生物，其不仅是细胞膜的重要组成成分，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，近些年来应用酵母细胞异源合成甾醇的研究不断深入。但由于甾醇是疏水性大分子，倾向于积累在酵母的膜结构中而引发细胞毒性，一定程度上限制了甾醇产量的进一步提升。因此，揭示酵母中甾醇转运机制，特别是与甾醇转运相关的转运蛋白的工作原理，有助于设计新的策略，解除酵母细胞工厂中的甾醇积累毒性、实现甾醇增产。酵母中甾醇转运主要通过蛋白质介导的非囊泡运输机制来完成，本文归纳了酵母中已报道的5类甾醇转运相关蛋白，即OSBP/ORPs家族蛋白、LAM家族蛋白、NPC样甾醇转运蛋白、ABC转运家族蛋白和CAP超家族蛋白，汇总了这些蛋白对细胞内甾醇梯度分布和稳态维持所起的重要作用。此外，本文还综述了甾醇转运蛋白在酵母细胞工厂中的应用现状。

Abstract:

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.