使用人工智能对微生物转胺酶进行热稳定性工程,并研究其潜在机制
Xiaoping Song1, Kai Han2, Pei Xu2
1College of Pharmacy, Anhui Institute of Medicine, Hefei, 230061, China. sxp20081012@sina.com.
Bioresources and bioprocessing
|March 7, 2026
概括
人工智能增强了酶的热稳定性. 机器学习预测微生物转质氨酶 (MTG) 突变改善了稳定性,S199E在半衰期和活性方面显示出最显著的收益.
科学领域:
- 生物化学 生物化学
- 计算生物学 计算生物学
- 蛋白质工程是指蛋白质工程.
背景情况:
- 人工智能 (AI) 正在彻底改变酶的分子进化.
- 整合机器学习 (ML) 与理性设计加速了蛋白质工程.
- 在将ML应用于酶修饰方面仍然存在挑战.
研究的目的:
- 实验验证ML预测的突变,以提高微生物转谷氨酶 (MTG) 的热稳定性.
- 通过模拟来研究改善热稳定的分子基础.
- 评估突变对酶活性和结合自由能量的影响.
主要方法:
- 稀疏卷积神经网络用于预测突变.
- 对E164L,E164P,S199E和S199Q突变物的实验验证.
- 模拟分子动力学以分析结构稳定性.
- 用LigPlot分析识别稳定性相互作用.
主要成果:
- 与野生型MTG相比,所有四种突变物都表现出显著增强的热稳定性.
- 突变S199E表现出最显著的改善,其半衰期分别是60°C和50°C的2.3倍和5.8倍.
- S199E显示酶活性增加了1.4倍,并通过键和盐桥增强了局部结构稳定性.
结论:
- 基于ML的合理设计有效地提高了酶的热稳定性.
- S199E突变通过局部结构增强提高了MTG的稳定性,而不是主要的形状变化.
- 这种方法为为工业应用设计强大的酶提供了一个有希望的策略.
更多相关视频
06:24Generic Protocol for Optimization of Heterologous Protein Production Using Automated Microbioreactor Technology
Published on: December 15, 2017
10.8K
11:51Engineering 'Golden' Fluorescence by Selective Pressure Incorporation of Non-canonical Amino Acids and Protein Analysis by Mass Spectrometry and Fluorescence
Published on: April 27, 2018
12.5K
相关概念视频
Tagging and Fusion Proteins
8.6K
Proteins are involved in several cellular processes and biochemical reactions. Analyzing a specific protein of interest requires it to be isolated from the other proteins in the cell. This is achieved by overexpressing the specific gene in a suitable host to produce large quantities of the target protein. A tag or label is recombined with the gene to produce a fusion protein containing the target protein and the tag. The tags on these fusion proteins can then be used for easy detection and...
8.6K
Conservative Site-specific Recombination and Phase Variation
7.1K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
7.1K
Factors Influencing Microbial Growth: Temperature
1.7K
Microorganisms display remarkable adaptations, enabling them to thrive in diverse ecological niches across a wide range of temperatures. Temperature profoundly influences microbial growth by affecting enzymatic activity, membrane fluidity, and other cellular processes.Each microorganism operates within a specific temperature range defined by three cardinal points: minimum, optimum, and maximum. Below the minimum temperature, membranes lose fluidity, halting transport processes. Above the...
1.7K
