酿酒酵母细胞融合机制及交配信号通路的合成生物学应用  

Mechanism of Yeast Mating Signal Pathway and Its Synthetic Biology Applications

作　　者：章益蜻 王宇娇 汪辰雨 刘颖[1] 仲森林 伍慧兰 刘冠楠 ZHANG Yi-Qing;WANG Yu-Jiao;WANG Chen-Yu;LIU Ying;ZHONG Sen-Lin;WU Hui-Lan;LIU Guan-Nan(College of Biotechnology and Pharmaceutical Engineering,Nanjing Tech University,Nanjing 211800,China;College of 2011,Nanjing Tech University,Nanjing 211800,China;School of Pharmaceutical Sciences,Nanjing Tech University,Nanjing 211800,China;Frontier Technology Research Institute,Tianjin University,Tianjin,301700,China)

机构地区：[1]南京工业大学生物与制药工程学院,南京211800 [2]南京工业大学2011学院,南京211800 [3]南京工业大学药学院,南京211800 [4]天津大学前沿技术研究院,天津301700

出　　处：《生物化学与生物物理进展》2023年第2期241-251,共11页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(21808109);江苏省自然科学基金(BK20180703);天津市自然科学基金(18JCQNJC10200);江苏省先进生物制造创新中心(XTD2214);国家级大学生创新创业训练计划(202110291065Z,202110291094Z)资助项目。

摘　　要：细胞融合是大多数真核生物发育中的一个基本生物过程。酿酒酵母作为真核生物基因组合成和转移的经典模式生物,其细胞融合机制不清楚,因此限制了它的合成生物学应用。在酿酒酵母的融合过程中,细胞对信息素做出反应,触发促分裂原活化的蛋白激酶(MAPK)级联反应以启动交配,随后细胞发生极化、细胞壁重塑、膜融合和核配。其中,研究可能的“融合酶”——受信息素调控的多跨膜蛋白(Prm1)为推动细胞融合可控性提供方向。酵母交配信号通路的合成生物学应用基于生物元件、生物装置与生物系统以及多细胞互作3个层次,本文分析了信息素诱导型启动子、G蛋白偶联受体、支架蛋白、转录因子、双稳态开关、调谐器、底盘细胞等在生物传感器及代谢工程等领域的应用。开发理性设计的模块化线路和优化交配途径来精确调控酵母交配的生理事件,对于细胞融合的人工可操纵性发展具有重要意义。Cell fusion is fundamental to various morphological and physiological events involved in the development of most eukaryotic organisms. Saccharomyces cerevisiae(S. cerevisiae) is a classic model organism for eukaryotic genome synthesis and transfer in the context of synthetic biology. However, the molecular mechanism underlying the yeast cell fusion remains to be fully understood, thereby limiting its synthetic biology application. In S. cerevisiae, mating initiates when cells respond to pheromones that trigger MAPK(mitogenactivated protein kinase) cascade, following with polarization, cell wall remodeling, membrane fusion, and karyogamy. This review discusses the current state of knowledge and progress regarding cell fusion in S. cerevisiae as well as the proteins involved in these events. Especially, the study of the possible “fusase” Prm1 provides a direction for promoting the manipulation of cell fusion. We further propose a hypothesis about the intracellular transport and maturation process of Prm1, which reasonably explains the regulation mechanism of site-directed aggregation of Prm1 at the plasma membrane. Notably, this review stresses the synthetic biology applications of yeast mating signaling pathway in biological components, biological devices and systems, and multicellular interactions. Such elements, including pheromone-responsive promoters, G protein-coupled receptors, scaffold proteins, transcription factors, bistable switches, tuners and chassis cells. Together they contribute to the applications of biosensors and metabolic engineering. Strategies such as rationally engineering of modular circuits and optimizing the reproductive pathway will promote the maneuverability of cell fusion.Moreover, many innovative synthetic biology tools, such as microfluidics, omics research, genome editing, and machine learning, allow researchers to examine the complex physiological activities and improve fusion efficiency. Our study lays foundation for the study of cell-fate decision system and the application o

关 键 词：酿酒酵母 细胞融合 Prm1 MAPK信号通路 合成生物学 启动子工程 生物传感器 机器学习 

分 类 号：Q819[生物学—生物工程]