Engineering the regioselectivity of Baeyer-Villiger monooxygenases

凭借这一奖项，化学部门的生命过程化学项目正在资助埃默里大学的Stefan Lutz博士，以创造具有增强区域选择性的Baeyer-Villiger氧化的新型生物催化剂。催化剂不仅促进工业过程中的化学反应，如生产石化燃料和制造药品，而且它们还控制着生命的化学反应，在驱动细胞中的生化反应中起着关键作用。更好地理解（生物）催化剂的基本原理，以及合成生物学和生物技术的进步，现在使科学家能够操纵和定制生物催化剂，使其具有诸如稳定性和对新物质的识别等特性。这些能力创造了前所未有的机会，使这些高效、可再生的催化剂适应工业应用中需要的新颖、非自然的功能，从而创造新的、更安全、更可持续的工艺。该项目将为研究生提供制备生物催化剂的专业培训，以及将其定制为特定的工业应用。它还向本科研究人员以及高中教师和学生介绍了生物催化和绿色化学的概念。风味酶工程在合成化学中的应用是一个发展成熟的领域。定向酶“进化”是一个新兴的领域，但这类酶的探索相对不足，但在化学领域具有巨大的应用潜力。采用黄素辅助因子类似物替代和蛋白质诱变的组合，天然单加氧酶将被定制为有效和选择性地将不对称酮转化为相应的酯区异构体。这些工程酶中的主要候选酶将通过全面的生化和生物物理分析进行表征。这些研究将提供有关各种工程策略影响的详细信息，并有助于为未来的酶重新设计努力开发准确的预测框架。

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Stefan Lutz from Emory University to create novel biocatalysts for Baeyer-Villiger oxidation with enhanced regio-selectivity. Catalysts not only facilitate chemical reactions in industrial processes as diverse as producing petrochemical fuels and manufacturing pharmaceuticals, but they also govern the chemistry of life, playing a key role in driving biochemical reactions in cells. A better understanding of the fundamentals of (bio)catalysts, as well as advances in synthetic biology and biotechnology now allow scientists to manipulate and tailor biocatalysts for properties such as stability and recognition of new substances. These capabilities have created unprecedented opportunities to adapt these highly efficient and renewable catalysts for novel, unnatural functions needed in industrial applications, thereby creating new, safer and more sustainable processes. This project will provide graduate students with specialized training in preparing biocatalysts, as well as tailoring them to specific industrial applications. It also introduces undergraduate researchers, as well as high school teachers and students to the concepts of biocatalysis and green chemistry. The area of flavo-enzyme engineering for utility in synthetic chemistry is one that is ripe for development. Directed enzyme 'evolution' is a burgeoning field, but this enzyme class is relatively underexplored, and yet holds great potential for application to chemistry of interest. Employing a combination of flavin cofactor analog substitution and protein mutagenesis, native monooxygenases will be tailored for effective and selective conversion of asymmetric ketones to the corresponding ester regio-isomers. Lead candidates among these engineered enzymes will be characterized via comprehensive biochemical and biophysical analysis. These studies will provide detailed information concerning the impact of various engineering strategies and assist in developing accurate predictive frameworks for future enzyme redesigning endeavors.