Enzymes involved in the degradation of aromatic compounds - mechanism, evolution and regulation

生命系统中发生的无数化学反应都是由酶催化的。大多数酶是蛋白质，它们折叠成紧凑的三维结构，创造了一个独特的环境，可以发生化学催化。因此，酶的结构对酶的功能有影响。S. Seah和他的学生们正在研究丙酮酸醛缩酶的这种结构-功能关系，这种酶可以独立进化以催化类似的反应。具体来说，他的团队正在确定这些醛缩酶是否利用类似的化学策略进行催化。他们还在研究这些醛缩酶如何调节其催化活性，并在代谢途径中与其他酶相互作用以确保效率。所研究的醛缩酶来自芳香族降解途径，可用于多氯联苯等有毒芳香族污染物的生物修复。醛缩酶也可用于合成药物化合物。正在研究的醛缩酶之一来自引起结核病的细菌，因此这项工作可能会导致对抗这种疾病的新药的开发。在更广泛的层面上，学习大自然如何创造新酶的原理将使我们能够应用这些知识来设计用于医学和工业的新型生物催化剂。这项研究工作也将有助于“功能基因组学”的新领域，使我们能够基于酶的构建模块（氨基酸）或3D折叠序列更准确地预测酶的功能。参与这项工作的本科生、研究生和博士后学员将学习使用分子生物学和生物化学的研究工具来解决科学问题。

The myriad of chemical reactions occurring within living systems are catalyzed by enzymes. Most enzymes are proteins which fold into a compact three dimensional structures, creating a unique environment where chemical catalysis can occur. Therefore, the structure of an enzyme has a bearing on function. S. Seah and his students are studying this structure-function relationship in enzymes known as pyruvate aldolases, that evolve independently to catalyze similar reactions. Specifically, his team is determining if these aldolases utilize similar chemical strategies for catalysis. They are also studying how some of these aldolases regulate their catalytic activity and interact with other enzymes in a metabolic pathway to ensure efficiency. The aldolases being studied are from aromatic degradation pathways that are useful for bioremediation of toxic aromatic pollutants, such as Polychlorinated biphenyls. Aldolases are also useful for the synthesis of pharmaceutical compounds. One of the aldolase being studied is from bacteria that cause tuberculosis, and therefore this work may lead o the development of new drugs against this disease. At the broader level, learning the principles of how nature creates new enzymes will allow us to apply this knowledge to design new biological catalysts for application in medicine and industry. The research work will also contribute to the new area of "functional genomics" allowing us to predict with greater accuracy the functions of enzymes based on the sequences of their building blocks (amino acids) or 3D fold. Undergraduate, graduate and postdoctoral trainees participating in this work will learn to solve scientific problems using research tools drawn from molecular biology and biochemistry.