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

合作研究：SusChEM：解锁油脂化学生产酶选择性的基本机制

• 批准号: 1703504
• 负责人: Brian Pfleger
• 金额: $ 30万
• 依托单位: University of Wisconsin-Madison
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1703504&HistoricalAwards=false
• 关键词: Collaborative; Research; SusChEM; Unlocking; fundamental

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.

工程，数学，生物化学和生物学相结合，以制定将可再生资源转化为更高价值的化学品和材料的战略。其中一些产品从未通过生物学方法生产，因此需要对生物体进行改造以使其成为可能。还非常需要能够预测对细胞蛋白质的有益修饰的计算工具，从而指导这些努力。该研究项目正在开发在脂肪和油的可持续生产中具有活性的新型蛋白质。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进程。本科生的研究经验和针对K-12学生和公众通过SCIENCountErs计划的推广工作正在提供，并有助于加强知识渊博的干劳动力的发展。 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，用于设计参与油脂化学代谢的新型酶。这种蛋白质设计基础设施正在整合分子建模和机器学习的最新发展，并开发设计规则，为三种油脂化学合成酶定制链长特异性。这些新的酶被部署在微生物生物催化剂中，并评估它们从可再生资源中生产油脂化学品的能力。最后，这项工作将产生一个更深入的了解选择性的油脂化学代谢，新型酶和微生物生物催化剂生产特种油脂化学品，酶的设计能力，可以广泛应用于合成生物学应用。

项目成果

EnZymClass: Substrate specificity prediction tool of plant acyl-ACP thioesterases based on ensemble learning

• DOI: 10.1016/j.crbiot.2021.12.002
• 发表时间: 2022-01-01
• 期刊: CURRENT RESEARCH IN BIOTECHNOLOGY
• 影响因子: 5.6
• 作者: Banerjee, Deepro;Jindra, Michael A.;Maranas, Costas D.
• 通讯作者: Maranas, Costas D.

Directed Evolution Reveals the Functional Sequence Space of an Adenylation Domain Specificity Code

定向进化揭示腺苷酸化域特异性代码的功能序列空间

• DOI: 10.1021/acschembio.9b00532
• 发表时间: 2019
• 期刊: ACS Chemical Biology
• 影响因子: 4
• 作者: Throckmorton, Kurt;Vinnik, Vladimir;Chowdhury, Ratul;Cook, Taylor;Chevrette, Marc G.;Maranas, Costas;Pfleger, Brian;Thomas, Michael George
• 通讯作者: Thomas, Michael George

Evaluation of strategies to narrow the product chain-length distribution of microbially synthesized free fatty acids

• DOI: 10.1016/j.ymben.2023.02.012
• 发表时间: 2023-03-10
• 期刊: METABOLIC ENGINEERING
• 影响因子: 8.4
• 作者: Jindra, Michael A.;Choe, Kisurb;Pfleger, Brian F.
• 通讯作者: Pfleger, Brian F.