Structural studies of Baeyer-Villiger monooxygenases

Baeyer-Villiger 单加氧酶的结构研究

• 批准号: 183867-2012
• 负责人: Berghuis, Albert
• 金额: $ 2.04万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=505805
• 关键词: Structural; studies; Baeyer; Villiger; monooxygenases; Structural; studies; Baeyer; Villiger; monooxygenases

Drugs are complex molecules that have very specific shapes. Pharmaceutical industry has been making these drugs using chemical reactions that frequently use toxic solvents and invariably create substantial waste. To address these issues that have environmental and financial implications, "green-chemistry" alternatives have been explored. One such alternative, is the use of "biocatalysts", i.e. enzymes that catalyze chemical reactions without the use of toxic solvents and that do not create excessive waste. Specifically, much attention has focused on "Baeyer-Villiger monooxygenases". Baeyer-Villiger monooxygenases are a class of enzymes found in bacteria that catalyze a type of reaction that is commonplace in the pharmaceutical industry. Employing these enzymes in an industrial setting will avoid the use of chlorinated solvents and acids, while limiting the amount of waste product produced. We have recently determined what these enzymes look like in atomic detail, using a method known as X-ray diffraction. Also, we have begun to examine how the atomic structure of these enzymes dictates their catalytic properties. Intriguingly, our initial studies have shown that the shape of the enzymes actually changes while they catalyze chemical reactions. We will continue to examine in atomic detail how Baeyer-Villiger monooxygenases catalyze chemical reactions, and how the changing shape facilitates this. This information will enable us to optimize these enzymes for very specific tasks that are of benefit to the pharmaceutical industry.

药物是具有非常特异的形状的复杂分子。 制药行业一直在使用经常使用有毒溶剂的化学反应制造这些药物，并且总是造成大量废物。 为了解决具有环境和财务影响的这些问题，已经探索了“绿色化学”替代方法。 一种替代方法是使用“生物催化剂”，即无需使用有毒溶剂而催化化学反应的酶，不会产生过多的废物。 具体而言，很多关注都集中在“ Baeyer-Villiger单加氧酶”上。 Baeyer-Villiger单加氧酶是细菌中发现的一类酶，可催化一种在制药行业中很常见的反应。 在工业环境中使用这些酶将避免使用氯化溶剂和酸，同时限制了产生的废物量。 我们最近使用称为X射线衍射的方法确定了原子细节中这些酶的样子。 同样，我们已经开始研究这些酶的原子结构如何决定其催化特性。 有趣的是，我们的初步研究表明，酶的形状在催化化学反应时实际上会发生变化。 我们将继续研究原子详细信息，Baeyer-Villiger单加仑酶如何催化化学反应，以及变化的形状如何促进这种反应。 这些信息将使我们能够针对对制药行业有益的非常具体的任务优化这些酶。