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

工程学、数学、生物化学和生物学结合在一起，开发出将可再生资源转化为更高价值的化学品和材料的策略。其中一些产品从未在生物上生产过，因此需要对生物体进行改造才能实现这一点。还非常需要计算工具来预测对细胞蛋白质的有益修饰，从而指导这些努力。这项研究项目正在开发新的蛋白质，这些蛋白质在脂肪和油的可持续生产中发挥积极作用。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不利于环境的进程。为本科生提供了研究经验，并通过SCIENCountErs计划向K-12学生和公众提供了外展工作，旨在促进具有高度知识的STEM劳动力的发展。这些努力正在加深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新陈代谢的新型酶。这个蛋白质设计基础设施正在整合分子建模和机器学习方面的最新发展，并为三种油脂化学合成酶定制链长特异性设计规则。这些新型酶被部署在微生物生物催化剂中，并对其从可再生资源中生产油脂化学品的能力进行了评估。总之，这项工作将加深对油脂化学代谢的选择性、生产特种油脂化学品的新型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的理解。

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.