Discovery and application of new halogenases
新型卤化酶的发现及应用
基本信息
- 批准号:10392879
- 负责人:
- 金额:$ 31.46万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-04-01 至 2024-03-31
- 项目状态:已结题
- 来源:
- 关键词:Active SitesAlkynesAmino AcidsAnabolismAnionsBinding ProteinsBiochemicalBioinformaticsBiologicalBiologyCarbonCatalysisCellsChemicalsChemistryComplexDevelopmentElectronsEngineeringEnzymesEvolutionFaceFamilyFamily memberFoundationsGenerationsGeometryGoalsHalogensHealthHumanHydrogen BondingHydroxylationIn VitroIndole AlkaloidsLibrariesLinkMetabolic BiotransformationMethodologyModificationMolecularNatural ProductsNatureOutcomePathway interactionsPeptidesPositioning AttributeProductionProtein EngineeringProteinsReactionRibosomesRouteSourceStructureTranslationsbasecatalystchemical functiondesignfunctional grouphalogenationimprovedin vivoinnovationinsightinterestnovelpublic health relevancerestraintscaffoldscreeningsmall moleculetool
项目摘要
Project Summary/Abstract
The rapid and modular generation of molecular diversity is key to the search for new chemical
functions. One particularly useful functional group is the halogen (X = Cl, Br, I), which enables
many selective and effective downstream strategies for creating structural complexity. In this
regard, halogenase enzymes have provided an important and complementary approach to
synthetic catalysts for regio- and stereoselective introduction of a halogen substituent on a
complex scaffold, which remains challenging to achieve. While many families of halogenases
exist, the radical halogenases provide the greatest potential for reaction diversity, as they are
competent to replace unactivated C-H bonds with a halogen unlike those that operate by
electrophilic or nucleophilic mechanisms. However, the substrate scope of these enzymes has
been limited to date to either protein-bound substrates or large late-stage natural product
intermediates. Our group has discovered a new clade of radical halogenases capable of reacting
with small molecule substrates. We now seek to take advantage of this discovery to develop new
tools for in vitro and in vivo synthesis. Specific aims of this proposal include: (i) elucidating the
structure and mechanism of these new radical halogenases, which will provide important insight
into their engineering, (ii) investigating and engineering selectivity in halogenases, and (iii)
developing applications for halogenases to produce new amino-acid based products.
项目总结/摘要
分子多样性的快速和模块化生成是寻找新化学品的关键
功能协调发展的一种特别有用的官能团是卤素(X = Cl、Br、I),其使得能够
许多选择性和有效的下游战略,以创造结构复杂性。在这
在这方面,卤化酶提供了一个重要的和补充的方法,
用于将卤素取代基区域选择性和立体选择性引入到
复杂的支架,这仍然具有挑战性。虽然许多卤化酶家族
存在,自由基卤化酶提供了反应多样性的最大潜力,因为它们是
能够用卤素取代未活化的C-H键,不像那些通过
亲电或亲核机制。然而,这些酶的底物范围具有
迄今仅限于蛋白质结合底物或大的晚期天然产物
中间体的我们的团队发现了一个新的自由基卤化酶分支,
用小分子底物。我们现在寻求利用这一发现开发新的
用于体外和体内合成的工具。这项建议的具体目标包括:
这些新的自由基卤化酶的结构和机制,这将提供重要的见解
(ii)研究和设计卤化酶的选择性,以及(iii)
开发卤化酶的应用以生产新的基于氨基酸的产品。
项目成果
期刊论文数量(0)
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{{ truncateString('MICHELLE C CHANG', 18)}}的其他基金
Discovery and mechanistic study of fluorine biochemistry
氟生物化学的发现及其机理研究
- 批准号:
8146802 - 财政年份:2011
- 资助金额:
$ 31.46万 - 项目类别:
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