Structural studies of Baeyer-Villiger monooxygenases

药物是高度复杂的分子，具有非常特殊的形状。制药业一直在使用化学反应来制造这些药物，这些化学反应经常需要有毒的溶剂，并且总是会产生大量的废物。为了解决这些对环境和财政有影响的问题，人们探索了“绿色化学”替代方案。其中一种替代方法是使用“生物催化剂”，即在不使用有毒溶剂的情况下催化化学反应且不会产生大量废物的酶。具体地说，人们非常关注Baeyer-Villiger单加氧酶，这种加氧酶催化精细化学工业中经常使用的反应，避免使用氯化溶剂和酸，同时限制产生的废物量。我们最近使用一种名为X射线衍射法的方法确定了这些酶的外观。此外，我们已经开始研究这些酶的形状如何决定催化性能。有趣的是，我们的初步研究表明，当这些酶催化化学反应时，它们的形状实际上会改变。我们将继续详细研究Baeyer-Villiger单加氧酶如何催化化学反应，以及不断变化的形状如何促进这一点。我们相信，有了这些信息，我们将能够为非常具体的任务优化酶，这些任务对精细化工，特别是制药行业是有利的。

Drugs are highly complex molecules that have very specific shapes. The pharmaceutical industry has been making these drugs using chemical reactions that frequently demand 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 substantial waste. Specifically, much attention has focused on Baeyer-Villiger monooxygenases, which catalyze reactions that are often used in the fine-chemical industry and which 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, using a method known as X-ray diffraction. Also, we have begun to examine how the shape of these enzymes dictates the 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. We believe that with this information we will be able to optimize the enzymes for very specific tasks that are of benefit to the fine-chemical and specifically the pharmaceutical industry.