Department of Biochemistry, Stanford University, Stanford, CA 94305, USA.
Department of Bioengineering and Therapeutic Sciences and Quantitative Biosciences Institute, University of California, San Francisco, CA 94158, USA.
Science. 2021 Mar 5;371(6533). doi: 10.1126/science.aay2784.
The mechanisms that underly the adaptation of enzyme activities and stabilities to temperature are fundamental to our understanding of molecular evolution and how enzymes work. Here, 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 across 1005 diverse bacterial enzyme families, suggesting widespread parallel adaptation to temperature. We assess the residue properties, molecular interactions, and interaction networks that appear to underly temperature adaptation.
酶活性和稳定性对温度适应的机制是我们理解分子进化以及酶如何工作的基础。在这里，我们通过对数千种酶进行深入的机制研究和全面的序列分析，研究了酶温度适应的分子和进化机制。我们表明，酮甾体异构酶（KSI）的温度适应主要源于一个残基的变化，其具有有限的局部上位性，并且我们确定了潜在的物理机制。这种残基变化发生在不同的 KSI 背景中，表明了对温度的平行适应。我们确定了与 1005 种不同细菌酶家族中的生物体生长温度相关的残基，这表明了广泛的对温度的平行适应。我们评估了似乎是温度适应基础的残基特性、分子相互作用和相互作用网络。
