Relationships between Substrate Promiscuity and Chiral Selectivity of Esterases from Phylogenetically and Environmentally Diverse Microorganisms
Relationships between Substrate Promiscuity and Chiral Selectivity of Esterases from Phylogenetically and Environmentally Diverse Microorganisms
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DOI：
10.3390/catal8010010
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发表时间：
2018-01-01
期刊：
影响因子：
3.9
通讯作者：
Ferrer, Manuel
中科院分区：
文献类型：
--
作者：
Coscolin, Cristina;Martinez-Martinez, Monica;Ferrer, Manuel
生物催化剂的底物特异性和选择性由蛋白质序列和活性位点的结构决定。寻找对多种底物起作用同时具有手性选择性的通用生物催化剂是制药和化学工业的兴趣所在。然而，这两个性质之间的关系在天然微生物酶仍然探索不足。在这里，我们进行了一组145个纯化的酯酶的底物混杂性和手性选择性的实验分析，从遗传和环境不同的微生物，这是对96个不同的酯，其中20个是对映异构体进行测定。我们的研究结果表明，底物混杂性和手性选择性之间的负相关性在评估的酶。酯酶显示出突出的底物混杂性和大的催化环境，其特征在于低手性选择性，这一特征具有有限的商业价值。尽管低水平的底物混杂性不能保证高的手性选择性，但具有较小活性位点的酯酶具有工业上感兴趣的手性选择性因子（>25）的概率显著高于混杂酶。总之，本研究明确地表明，混杂和选择性酯酶似乎是罕见的性质和底物混杂可以用作酯酶的手性选择性水平的指标，反之亦然。
Substrate specificity and selectivity of a biocatalyst are determined by the protein sequence and structure of its active site. Finding versatile biocatalysts acting against multiple substrates while at the same time being chiral selective is of interest for the pharmaceutical and chemical industry. However, the relationships between these two properties in natural microbial enzymes remain underexplored. Here, we performed an experimental analysis of substrate promiscuity and chiral selectivity in a set of 145 purified esterases from phylogenetically and environmentally diverse microorganisms, which were assayed against 96 diverse esters, 20 of which were enantiomers. Our results revealed a negative correlation between substrate promiscuity and chiral selectivity in the evaluated enzymes. Esterases displaying prominent substrate promiscuity and large catalytic environments are characterized by low chiral selectivity, a feature that has limited commercial value. Although a low level of substrate promiscuity does not guarantee high chiral selectivity, the probability that esterases with smaller active sites possess chiral selectivity factors of interest for industry (>25) is significantly higher than for promiscuous enzymes. Together, the present study unambiguously demonstrates that promiscuous and selective esterases appear to be rare in nature and that substrate promiscuity can be used as an indicator of the chiral selectivity level of esterases, and vice versa.