Collaborative Research: SusChEM: Unlocking the fundamental mechanisms that underlie selectivity in oleochemical producing enzymes

将工程、数学、生物化学和生物学结合起来，制定将可再生资源转化为高价值化学品和材料的策略。其中一些产品从未以生物方式生产过，因此需要对生物体进行改造以使其成为可能。我们还非常需要能够预测细胞蛋白有益修饰的计算工具，从而指导这些工作。这个研究项目正在开发一种新型蛋白质，这种蛋白质在脂肪和油的可持续生产中很活跃。如果成功，这项工作有可能取代导致热带地区森林砍伐的不可持续和对环境不利的过程。为本科生提供研究经验，并通过SCIENCountErs项目向K-12学生和公众提供推广工作，以促进高知识STEM劳动力的发展。这些努力增强了我们对蛋白质设计的技术、能力和局限性的理解。在这个合作研究项目中，研究人员正在整合计算和实验方法来开发软件，该软件将用于设计涉及油脂化学代谢的新型酶。这种蛋白质设计基础设施整合了分子建模和机器学习的最新发展，并为三种油化学合成酶制定了定制链长特异性的设计规则。这些新型酶正在应用于微生物生物催化剂中，并对其从可再生资源中产生油脂化学物质的能力进行了评估。总之，这项工作将使人们对油脂化学代谢的选择性、生产特殊油脂化学物质的新酶和微生物生物催化剂以及可广泛应用于合成生物学应用的酶设计能力有更深入的了解。

Engineering, mathematics, biochemistry, and biology are combined to develop strategies for converting renewable resources into higher-value chemicals and materials. Some of these products have never been produced biologically, so organisms need to be modified to make this possible. There is also a great need for computational tools that can predict beneficial modifications to cellular proteins, thereby guiding these efforts. This research project is developing novel proteins that are active in the sustainable production of fats and oils. If successful, this work has the potential to displace unsustainable and environmentally unfriendly processes that contribute to the deforestation of tropical regions. Research experiences for undergraduate students and outreach efforts directed at K-12 students and the public through the SCIENCountErs program are being provided and serve to enhance the development of a highly knowledgeable STEM workforce. The efforts are enhancing our understanding of the techniques, capabilities, and limitations of protein design. In this collaborative research project, researchers are integrating computational and experimental methods to develop software that will be used to design novel enzymes involved in oleochemical metabolism. This protein-design infrastructure is integrating recent developments in molecular modeling and machine learning and developing design rules for tailoring chain length specificity for three oleochemical-synthesizing enzymes. These novel enzymes are being deployed in microbial biocatalysts and evaluated for their ability to produce oleochemicals from renewable resources. Upon conclusion, this work will generate a deeper understanding of selectivity in oleochemical metabolism, novel enzymes and microbial biocatalysts for producing specialty oleochemicals, and enzyme-design capabilities that could be widely applied in synthetic biology applications.