RUI: The Sources of Substrate Specificity in Hydroquinone Dioxygenases

这个生命过程化学（CLP）项目的奖项是与分子和细胞生物科学部（MCB）共同资助的，支持惠特曼学院的Tim Machonkin教授的工作，以了解某些酶如何结合并在氯化对苯二酚上进行化学转化的基本决定因素。一些细菌有非凡的能力分解稳定的芳香族化合物，包括在极少数情况下氯化芳香族。某些类型的含铁酶参与了这些过程。研究最少的是那些专门识别和切割氯化对苯二酚的基因。这些对苯二酚双加氧酶似乎是最近才进化出来的，以降解从人类活动中进入环境的合成化合物。决定这些酶如何特异性识别并对氯代对苯二酚进行环切割反应的因素尚不清楚。因此，对苯二酚双加氧酶提供了一个理想的平台来学习蛋白质如何特异性地结合氯化分子并激活它们进行化学转化，以及金属酶（如含铁环切割酶）如何进化出新的功能。这项工作将使大量本科生沉浸在涉及一系列技术的尖端生化研究中，促进这所主要的本科院校的教学和研究的整合。从这项研究中获得的知识可以应用于其他类型的含铁酶，包括芳香分子的分解，并可能导致具有新特性的酶的工程。这反过来又可以改进氯化芳香分子的生物修复方法，这是常见的难以处理的环境污染物。

This award in the Chemistry of Life Processes (CLP) program, co-funded with the Division of Molecular and Cellular Biosciences (MCB), supports work by Professor Tim Machonkin at Whitman College to understand the fundamental determinants of how certain enzymes bind and carry out chemical transformations on chlorinated hydroquinones. Some bacteria have the remarkable ability to break down stable aromatic compounds, including in rare cases chlorinated aromatics. Certain types of iron-containing enzymes are involved in these processes. Among the least studied are ones that specifically recognize and cleave chlorinated hydroquinones. These hydroquinone dioxygenases appear to have evolved recently to degrade synthetic compounds that entered the environment from human activity. The factors that determine how these enzymes specifically recognize and carry out the ring-cleaving reaction on chlorinated hydroquinones are unknown. Thus, hydroquinone dioxygenases provide an ideal platform for learning how proteins can specifically bind chlorinated molecules and activate them for chemical transformations, as well as how metalloenzymes (such as iron-containing ring-cleaving enzymes) evolve new functions.This work will immerse a significant number of undergraduate students in cutting-edge biochemical research involving an array of techniques, promoting the integration of teaching and research at this primarily undergraduate institution. The knowledge gained from this research could be applied to other classes of iron-containing enzymes involved the breakdown of aromatic molecules, and could lead to engineering of enzymes with novel properties. This, in turn, could lead to improved methods for bioremediation of chlorinated aromatic molecules, which are common intractable environmental pollutants.