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.
项目摘要/摘要
分子多样性的快速和模块化生成是寻找新化学物质的关键
功能。一个特别有用的官能团是卤素(X=氯、溴、碘),它能够
许多有选择和有效的下游战略,以创造结构复杂性。在这
在这方面,卤素酶提供了一种重要的补充方法
用于区域和立体选择性引入卤素取代基的合成催化剂
复杂的脚手架,这仍然是具有挑战性的实现。而卤素酶的许多家族
自由基卤化酶的存在为反应多样性提供了最大的潜力,因为它们
有能力用卤素取代未活化的C-H键,而不是通过
亲电或亲核机制。然而,这些酶的底物范围有
仅限于蛋白质结合的底物或大型后期天然产品
中间体。我们小组发现了一类新的自由基卤化酶
用小分子底物。我们现在寻求利用这一发现开发新的
体外和体内合成的工具。这项建议的具体目的包括:(I)澄清
这些新的自由基卤化酶的结构和机制,将提供重要的见解
(2)卤代酶的选择性研究和工程设计;(3)
开发卤化酶在生产新的氨基酸产品方面的应用。
项目成果
期刊论文数量(0)
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会议论文数量(0)
专利数量(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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