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

基本信息

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

项目摘要

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，生物化学和生物学结合在一起，以制定将可再生资源转化为高价值化学品和材料的策略。这些产品中的一些从未在生物学上生产，因此需要修改生物以使其成为可能。还需要计算工具，可以预测对细胞蛋白的有益修改，从而指导这些努力。该研究项目正在开发活跃于脂肪和油的可持续生产中的新型蛋白质。如果成功的话，这项工作有可能取代有助于热带地区森林砍伐的不可持续和环境不友好的过程。正在提供针对K-12学生和公众通过Sciencounters计划的本科生和外展工作的研究经验，并有助于增强知识渊博的STEM劳动力的发展。这些努力正在增强我们对蛋白质设计技术，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，以开发软件，该软件将用于设计涉及油化学代谢的新型酶。该蛋白质设计基础设施正在整合分子建模和机器学习中的最新发展，并开发了设计规则，以针对三种油化学合成酶调整链长特异性。这些新型酶正在微生物生物催化剂中部署，并评估了它们从可再生资源中生产油化学物质的能力。结论是，这项工作将对油化化代谢，新型酶和微生物生物催化剂的选择性产生更深入的了解，用于生产特种油化学物质，以及酶设计能力，这些能力可以广泛应用于合成生物学应用中。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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

Revisiting metabolic engineering strategies for microbial synthesis of oleochemicals