CAREER: Accessing Chemical Diversity through the Characterization and Redesign of Natural Product Synthases

有了这个奖项，化学系的生命过程化学计划正在资助哈弗福德学院的路易丝·查库迪安博士，让本科生通过学习和应用自然界的经验教训来发现化学多样性的新途径。 自然界已经进化出非常简单的路线来制造非常复杂的分子，其中许多分子太复杂，无法在实验室中合成。 资助的研究重点是表征最古老和独特的生物合成途径的化学，这些途径尚未被科学家探索。 实验程序导致识别自然界编码的新化合物和酶，以及新工具，使工程的天然途径，以建立新的结构和功能的分子。 该项目还整合了一个专业发展系列，使本科生接触到化学科学的毕业后就业机会，以及BioArt外展活动，利用有色细菌来说明化学和生物学的基本概念。该研究通过对未开发的聚酮合酶（PKS）的表征，让本科生参与发现化学多样性的新生物合成路线基因簇和酶。孤儿II型（聚芳族）聚酮基因簇从不同的门的特点是阐明化学多样性编码的古老的非放线菌物种。 这些细菌菌种被评价为PKS酶的来源，其可以在易处理的异源宿主中表达，以实现对知之甚少的II型PKS的体外表征。 最后，酰基载体蛋白（ACP）代表PKS进化的不同阶段的特点是使用传统的和创新的生物化学和生物物理方法相结合。结果将导致识别新的化学多样性编码的性质，以及新的工具，使生物合成工程的混合PKS。 这项工作还包括由学生主导的未表征的生物合成基因簇的注释，一个专业发展系列，让学生接触到科学领域的毕业后职业机会，以及利用聚酮化合物产生细菌的色素性质的BioArt外展活动。 外联活动向来自不同文化和社会经济背景的青年学生以及有智力和发育残疾的成年人介绍化学和生物学概念。

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Louise Charkoudian from Haverford College to engage undergraduates in the discovery of new routes to chemical diversity by learning and applying lessons from nature. Nature has evolved remarkably simple routes to make very complicated molecules, many of which are too complex to be readily synthesized in the laboratory. The funded research focuses on characterizing the chemistry of the most ancient and unique biosynthetic pathways, which have yet to be explored by scientists. The experimental procedures lead to the identification of new compounds and enzymes encoded by nature, as well as new tools to enable the engineering of natural pathways to build molecules of novel structure and function. This project also integrates a professional development series to expose undergraduate students to post-graduation career opportunities in the chemical sciences, as well as BioArt outreach activities that employ pigmented bacteria to illustrate fundamental concepts of chemistry and biology.The research engagees undergraduates in the discovery of new biosynthetic routes to chemical diversity through the characterization of unexplored polyketide synthase (PKS) gene clusters and enzymes. Orphaned type II (polyaromatic) polyketide gene clusters from diverse phyla are characterized to elucidate the chemical diversity encoded by ancient non-actinomycete species. These bacterial species are evaluated as a source of PKS enzymes that can be expressed in tractable heterologous hosts to enable in vitro characterization of poorly understood type II PKSs. Finally, acyl carrier proteins (ACPs) representing diverse stages of PKS evolution are characterized using a combination of traditional and innovative biochemical and biophysical methods. Results will lead to the identification of new chemical diversity encoded by nature, as well as new tools to enable the biosynthetic engineering of hybrid PKSs. The work also includes the student-led annotation of uncharacterized biosynthetic gene clusters, a professional development series to expose students to post-graduation career opportunities in the sciences, and BioArt outreach activities that leverage the pigmented nature of polyketide-producing bacteria. The outreach activities introduce concepts of chemistry and biology to young students from diverse cultural and socioeconomic backgrounds, as well as to adults with intellectual and developmental disabilities.