Parallel molecular mechanisms for enzyme temperature adaptation

The mechanisms that underly the adaptation enzyme activities and stabilities to temperature are fundamental to our understanding of molecular evolution and how enzymes work. Herein, we investigate the molecular and evolutionary mechanisms of enzyme temperature adaption, combining deep mechanistic studies with comprehensive sequence analyses of thousands of enzymes. We show that temperature adaptation in ketosteroid isomerase (KSI) arises primarily from one residue change with limited, local epistasis and we establish the underlying physical mechanisms. This residue change occurs in diverse KSI backgrounds, suggesting parallel adaptation to temperature. We identify residues associated with organismal growth temperature in 1005 diverse bacterial enzyme families, suggesting widespread parallel adaptation. We assess the properties of these residues, molecular interactions and interaction networks that appear to underly temperature adaptation.酶活性与稳定性的温度适应性机制，是我们理解分子进化及酶促功能本质的核心基础。本研究结合深度机制解析与数千种酶的全面序列分析，探究了酶温度适应性的分子与进化机制。研究表明，酮类固醇异构酶（ketosteroid isomerase, KSI）的温度适应性主要源于单个氨基酸残基的改变，且仅伴随有限的局部上位性（epistasis），并阐明了其背后的物理机制。该氨基酸残基改变在多种不同的KSI遗传背景中均有出现，提示其存在针对温度的平行适应性进化。我们在1005个多样化的细菌酶家族中，鉴定出了与生物体生长温度相关的氨基酸残基，这表明温度适应性的平行进化广泛存在。我们系统剖析了这些残基的特性、分子相互作用模式以及潜在介导温度适应性的互作网络。