Collaborative Research: Mechanism-guided enzyme engineering for fucosylated glycoconjugate synthesis

合作研究:机制引导的岩藻糖基化糖复合物合成酶工程

基本信息

项目摘要

Glycosynthases are enzymes that have been engineered to make instead of break chains of complex sugars (oligosaccharides and carbohydrates). With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Heather Mayes from the University of Michigan and Dr. Shishir Chundawat from Rutgers University to uncover how glycosynthases synthesize prebiotic oligosaccharides or carbohydrates. These enzymes fill a pressing need in research and industrial biotechnology for the ability to produce designer carbohydrates, sugars that are designed for a specific purpose. There remains, however, a lack mechanistic understanding for how to better engineer glycosynthases to be highly specific and efficient in making complex sugars. This project combines computational and experimental studies to provide a mechanistic understanding of how a glycosynthase (alpha-L-fucosidase) catalyzes creation of specific oligosaccharides, which will in turn enable rational design of enzymes to make designer carbohydrates. The broader impacts include designing efficient routes for creating human milk oligosaccharides that could be included in infant formula to bring the composition closer to that of human milk. Human milk oligosaccharides can improve human health by promoting growth of beneficial gut bacteria and lowering incidences of other pathogenic infections. The software developed in this work for designing such enzymes will be made publicly available. Finally, the studies form the basis for outreach activities that use the biochemistry of carbohydrates to engage with students from under-resourced communities in Michigan and New Jersey.The overall goal of this project is to understand how alpha-L-fucosidases synthesize simple glycoconjugates (e.g., human milk oligosaccharides). The hypothesis to be tested is that a priori analysis of enzyme active and binding sites, based on sequence and structural data, can be used to predict mutations that will eliminate the hydrolysis activity of the enzyme in favor of glycosidic bond synthesis of bespoke oligosaccharides. The objectives of this project are to: 1) employ experimental and computational studies to identify key structural properties that determine whether a particular enzyme mutant will be an active glycosynthase; 2) create automated processes to predict and test which mutants of disparate enzymes will be active fucosynthases; and 3) predict and test mutations needed to alter substrate specificity. The results of this feasibility study will advance the path to production of a broad suite of oligosaccharides not currently readily available for research and/or commercial applications.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
糖合酶是经过改造的酶,用于制造而不是破坏复杂糖(低聚糖和碳水化合物)的链。有了这个奖项,化学部的生命过程化学计划正在资助密歇根大学的石楠梅耶斯博士和罗格斯大学的Shishir Chundawat博士,以揭示糖苷酶如何合成益生元寡糖或碳水化合物。这些酶满足了研究和工业生物技术对生产设计师碳水化合物的迫切需求,这些碳水化合物是为特定目的而设计的糖。然而,对于如何更好地将糖苷酶工程化为在制备复合糖中高度特异性和有效的,仍然缺乏机理上的理解。该项目结合了计算和实验研究,以提供对糖合酶(α-L-岩藻糖苷酶)如何催化产生特定寡糖的机理理解,这反过来又使酶的合理设计能够制造设计师碳水化合物。更广泛的影响包括设计生产母乳低聚糖的有效途径,这些低聚糖可以包含在婴儿配方奶粉中,使其成分更接近母乳。人乳低聚糖可以通过促进有益肠道细菌的生长和降低其他病原体感染的发生率来改善人类健康。在这项工作中开发的用于设计这种酶的软件将公开提供。最后,这些研究形成了利用碳水化合物的生物化学与密歇根州和新泽西资源不足社区的学生接触的外展活动的基础。该项目的总体目标是了解α-L-岩藻糖苷酶如何合成简单的糖缀合物(例如,人乳低聚糖)。待检验的假设是,基于序列和结构数据的酶活性和结合位点的先验分析可用于预测突变,该突变将消除酶的水解活性,有利于定制寡糖的糖苷键合成。该项目的目标是:1)采用实验和计算研究来确定决定特定酶突变体是否为活性糖合酶的关键结构特性; 2)创建自动化过程来预测和测试不同酶的哪些突变体将是活性岩藻糖苷酶; 3)预测和测试改变底物特异性所需的突变。这项可行性研究的结果将推动目前尚未用于研究和/或商业应用的一系列低聚糖的生产。该奖项反映了NSF的法定使命,并被认为值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估来支持。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Ronald Larson其他文献

Validity of the bead-spring model for describing the linear viscoelastic properties of single-strand DNA under strongly denaturing conditions
  • DOI:
    10.1007/s00397-007-0197-4
  • 发表时间:
    2007-06-12
  • 期刊:
  • 影响因子:
    3.000
  • 作者:
    Semant Jain;Ronald Larson
  • 通讯作者:
    Ronald Larson

Ronald Larson的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Ronald Larson', 18)}}的其他基金

Modelling extensional flow properties of solutions of polymers and thread-like micelles
模拟聚合物和线状胶束溶液的拉伸流动特性
  • 批准号:
    2323147
  • 财政年份:
    2023
  • 资助金额:
    $ 27万
  • 项目类别:
    Standard Grant
Cracking the Mystery of Polyelectrolyte Coacervate Structure and Dynamics
破解聚电解质凝聚层结构和动力学之谜
  • 批准号:
    2100513
  • 财政年份:
    2021
  • 资助金额:
    $ 27万
  • 项目类别:
    Standard Grant
2022 GRC / GRS on Colloidal, Macromolecular, and Polyelectrolyte Solutions: Sub-title: “Connecting theory and simulations to experiments and applications.”
2022 年关于胶体、高分子和聚电解质解决方案的 GRC / GRS:副标题:“将理论和模拟与实验和应用联系起来。”
  • 批准号:
    2134789
  • 财政年份:
    2021
  • 资助金额:
    $ 27万
  • 项目类别:
    Standard Grant
Linear and Nonlinear Rheology of Thread-like Micelles: Multi-scale Simulations, Theory, and Experiments
线状胶束的线性和非线性流变学:多尺度模拟、理论和实验
  • 批准号:
    1907517
  • 财政年份:
    2019
  • 资助金额:
    $ 27万
  • 项目类别:
    Standard Grant
Polyelectrolyte Phase Behavior and Transport
聚电解质相行为和传输
  • 批准号:
    1707640
  • 财政年份:
    2017
  • 资助金额:
    $ 27万
  • 项目类别:
    Standard Grant
Integrated multi-scale, multi-tool, modeling of transport in polymer-colloid assemblies
聚合物胶体组件中集成的多尺度、多工具传输建模
  • 批准号:
    1602183
  • 财政年份:
    2016
  • 资助金额:
    $ 27万
  • 项目类别:
    Standard Grant
UNS: Multi-scale Simulations of Branched Thread-like Micelles
UNS:支化线状胶束的多尺度模拟
  • 批准号:
    1500377
  • 财政年份:
    2015
  • 资助金额:
    $ 27万
  • 项目类别:
    Standard Grant
Constraint Release Dynamics in Entangled Polymers
缠结聚合物中的约束释放动力学
  • 批准号:
    1403335
  • 财政年份:
    2014
  • 资助金额:
    $ 27万
  • 项目类别:
    Standard Grant
Planning Grant: I/UCRC for The Center for Macromolecular Topology (CMT)
规划资助:I/UCRC 高分子拓扑中心 (CMT)
  • 批准号:
    1134788
  • 财政年份:
    2011
  • 资助金额:
    $ 27万
  • 项目类别:
    Standard Grant
Collaborative Research: Towards a Molecular-Scale Understanding of Flow-Induced Gelation in Thread-Like Micelle Solutions
合作研究:对线状胶束溶液中流动诱导凝胶化的分子尺度理解
  • 批准号:
    0853662
  • 财政年份:
    2009
  • 资助金额:
    $ 27万
  • 项目类别:
    Continuing Grant

相似国自然基金

Research on Quantum Field Theory without a Lagrangian Description
  • 批准号:
    24ZR1403900
  • 批准年份:
    2024
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
Cell Research
  • 批准号:
    31224802
  • 批准年份:
    2012
  • 资助金额:
    24.0 万元
  • 项目类别:
    专项基金项目
Cell Research
  • 批准号:
    31024804
  • 批准年份:
    2010
  • 资助金额:
    24.0 万元
  • 项目类别:
    专项基金项目
Cell Research (细胞研究)
  • 批准号:
    30824808
  • 批准年份:
    2008
  • 资助金额:
    24.0 万元
  • 项目类别:
    专项基金项目
Research on the Rapid Growth Mechanism of KDP Crystal
  • 批准号:
    10774081
  • 批准年份:
    2007
  • 资助金额:
    45.0 万元
  • 项目类别:
    面上项目

相似海外基金

Collaborative Research: Understanding the discharge mechanism at solid/aprotic interfaces of Na-O2 battery cathodes to enhance cell cyclability
合作研究:了解Na-O2电池阴极固体/非质子界面的放电机制,以增强电池的循环性能
  • 批准号:
    2342025
  • 财政年份:
    2024
  • 资助金额:
    $ 27万
  • 项目类别:
    Standard Grant
Collaborative Research: EAGER: Designing Nanomaterials to Reveal the Mechanism of Single Nanoparticle Photoemission Intermittency
合作研究:EAGER:设计纳米材料揭示单纳米粒子光电发射间歇性机制
  • 批准号:
    2345581
  • 财政年份:
    2024
  • 资助金额:
    $ 27万
  • 项目类别:
    Standard Grant
Collaborative Research: EAGER: Designing Nanomaterials to Reveal the Mechanism of Single Nanoparticle Photoemission Intermittency
合作研究:EAGER:设计纳米材料揭示单纳米粒子光电发射间歇性机制
  • 批准号:
    2345582
  • 财政年份:
    2024
  • 资助金额:
    $ 27万
  • 项目类别:
    Standard Grant
Collaborative Research: EAGER: Designing Nanomaterials to Reveal the Mechanism of Single Nanoparticle Photoemission Intermittency
合作研究:EAGER:设计纳米材料揭示单纳米粒子光电发射间歇性机制
  • 批准号:
    2345583
  • 财政年份:
    2024
  • 资助金额:
    $ 27万
  • 项目类别:
    Standard Grant
Collaborative Research: Understanding the discharge mechanism at solid/aprotic interfaces of Na-O2 battery cathodes to enhance cell cyclability
合作研究:了解Na-O2电池阴极固体/非质子界面的放电机制,以增强电池的循环性能
  • 批准号:
    2342024
  • 财政年份:
    2024
  • 资助金额:
    $ 27万
  • 项目类别:
    Standard Grant
Collaborative Research: Integrated experiments and simulations to understand the mechanism and consequences of polymer adsorption in films and nanocomposites
合作研究:综合实验和模拟来了解薄膜和纳米复合材料中聚合物吸附的机制和后果
  • 批准号:
    2312325
  • 财政年份:
    2023
  • 资助金额:
    $ 27万
  • 项目类别:
    Standard Grant
Collaborative Research: Metabolic Bet-Hedging as a mechanism for the maintenance of functional diversity in tree-ectomycorrhizal mutualisms
合作研究:代谢下注对冲作为维持树外生菌根互利共生功能多样性的机制
  • 批准号:
    2316522
  • 财政年份:
    2023
  • 资助金额:
    $ 27万
  • 项目类别:
    Standard Grant
Collaborative Research: Bioinspired High Energy Recycling Mechanism Ankle Foot Prosthesis
合作研究:仿生高能回收机制踝足假肢
  • 批准号:
    2231031
  • 财政年份:
    2023
  • 资助金额:
    $ 27万
  • 项目类别:
    Standard Grant
Collaborative Research: Bioinspired High Energy Recycling Mechanism Ankle Foot Prosthesis
合作研究:仿生高能回收机制踝足假肢
  • 批准号:
    2231032
  • 财政年份:
    2023
  • 资助金额:
    $ 27万
  • 项目类别:
    Standard Grant
Collaborative Research: Overlooked Oxidation of Aqueous Alcohols: Kinetics, Mechanism, and Relevance to Water Reuse
合作研究:被忽视的水醇氧化:动力学、机制以及与水回用的相关性
  • 批准号:
    2304861
  • 财政年份:
    2023
  • 资助金额:
    $ 27万
  • 项目类别:
    Continuing Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了