Finch Anthony J, Kim Jin Ryoun
Department of Chemical and Biomolecular Engineering, New York University, 6 MetroTech Center, Brooklyn, NY 11201, USA.
Microorganisms. 2018 Sep 25;6(4):97. doi: 10.3390/microorganisms6040097.
Literature from the past two decades has outlined the existence of a trade-off between protein stability and function. This trade-off creates a unique challenge for protein engineers who seek to introduce new functionality to proteins. These engineers must carefully balance the mutation-mediated creation and/or optimization of function with the destabilizing effect of those mutations. Subsequent research has shown that protein stability is positively correlated with "evolvability" or the ability to support mutations which bestow new functionality on the protein. Since the ultimate goal of protein engineering is to create and/or optimize a protein's function, highly stable proteins are preferred as potential scaffolds for protein engineering. This review focuses on the application potential for thermophilic proteins as scaffolds for protein engineering. The relatively high inherent thermostability of these proteins grants them a great deal of mutational robustness, making them promising scaffolds for various protein engineering applications. Comparative studies on the evolvability of thermophilic and mesophilic proteins have strongly supported the argument that thermophilic proteins are more evolvable than mesophilic proteins. These findings indicate that thermophilic proteins may represent the scaffold of choice for protein engineering in the future.
过去二十年的文献已经概述了蛋白质稳定性和功能之间存在权衡。这种权衡给试图为蛋白质引入新功能的蛋白质工程师带来了独特的挑战。这些工程师必须谨慎地平衡突变介导的功能创造和/或优化与这些突变的去稳定化效应。后续研究表明，蛋白质稳定性与“进化能力”呈正相关，“进化能力”即支持赋予蛋白质新功能的突变的能力。由于蛋白质工程的最终目标是创造和/或优化蛋白质的功能，高度稳定的蛋白质作为蛋白质工程的潜在支架更受青睐。本综述聚焦于嗜热蛋白质作为蛋白质工程支架的应用潜力。这些蛋白质相对较高的固有热稳定性赋予它们很大的突变稳健性，使其成为各种蛋白质工程应用的有前景的支架。对嗜热蛋白质和中温蛋白质进化能力的比较研究有力地支持了嗜热蛋白质比中温蛋白质更具进化能力这一观点。这些发现表明，嗜热蛋白质可能代表未来蛋白质工程的首选支架。
