New Methodologies for Accelerating Natural Product Discovery
加速天然产品发现的新方法
基本信息
- 批准号:8129632
- 负责人:
- 金额:$ 36.93万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-08-15 至 2013-05-31
- 项目状态:已结题
- 来源:
- 关键词:Actinobacteria classAddressAdoptedAreaBiodiversityBiologicalBiological FactorsBiological PreservationChargeChemicalsComplementComplexComputing MethodologiesCrude ExtractsDataDevelopmentDimensionsEcosystemEmerging TechnologiesEnzymesGasesGenomicsGoalsIn SituIonsMapsMass Spectrum AnalysisMeasuresMetabolicMethodologyMethodsMinorMolecularMolecular BankMolecular ConformationMolecular StructureMyxococcalesNatural Products ChemistryOrganismPeptidesPharmaceutical PreparationsPhaseProcessProductionPropertyPubChemRequest for ApplicationsResearch PersonnelSavingsScreening procedureSourceStructureTechniquesTechnologyTimeUnited States National Institutes of HealthUniversitiesanalytical methodbasecryogenicsinnovationinterestion mobilitymicrobialmicroorganismmolecular massprogramspublic health relevancereceptorrepositoryresponsesmall moleculesmall molecule librariestooltwo-dimensional
项目摘要
DESCRIPTION (provided by applicant): This application is in response to a Request for Applications for New Methodologies in Natural Product Chemistry (RFA-RM-09-005). We propose a campaign to establish a new program of natural product discovery based on a) a new biological source in the form of cave derived microorganisms and b) a new analytical method based on ion mobility mass spectrometry (IM-MS). These two aspects will open up a new reservoir of biodiversity for the discovery of natural products and provide a new method to accelerate the discovery of compounds in crude extracts and reduce the labor involved in their isolation. The labor and time savings derive from the ability to prioritize metabolites for isolation and structure elucidation based on their IM-MS measured properties. Aim 1. Develop natural product analysis using ion mobility mass spectroscopy (IM-MS). IM-MS is a form of 2-dimensional mass spectrometry that plots both mass/charge ratio and gas-phase collision cross- sectional area, which may be directly related to molecular conformation and functionality. We will evaluate the correlation of mass-collision area ratio to natural product class and compare these correlations to computationally predicted values. These data will map compound structure, class and conformation to IM-MS values. Aim 2. Develop cave microorganisms as a new source of natural product diversity. The isolation, cryogenic preservation and genotaxonomic characterization of culturable hypogean myxobacteria and actinobacteria will provide a new reservoir for natural product discovery and a source of extract material for the subsequent aims. Aim 3. Develop IM-MS as a method to identify candidates in extracts. A subset of taxonomically unique organisms will be evaluated for secondary metabolic potential by IM-MS. Compounds with IM-MS properties that distinguish compound class, functionality or unique conformation will be targeted for isolation/structure elucidation. The aims are parallel, but synergistic. New methods for identifying secondary metabolites from complex sources are essential for accelerating discovery. New sources of biodiversity are continuously needed to expand access to their biosynthetic molecular diversity. Cave microorganisms will provide a biological source of extracts needed to develop IM-MS as tool for identification of secondary metabolites in extracts. The natural products discovered by proposed methodologies will be available to the NIH Molecular Libraries Program (MLP) including Molecular Libraries Probe Production Centers Network (MLPCN), Molecular Libraries Small- Molecule Repository (MLSMR) and PubChem.
PUBLIC HEALTH RELEVANCE: Natural products are an excellent source for drugs, but they are difficult to discover as they must be identified as minor components of complex extracts from biological sources. We propose to develop two-dimensional separations on the basis of molecular structure and mass to guide the identification of natural products from complex biological sources. Furthermore, cave derived microorganisms, a previously untapped source of biodiversity, will be investigated for natural product discovery.
描述(由申请人提供):本申请是对天然产物化学新方法申请请求(RFA-RM-09-005)的回应。我们提出了一项运动,建立一个新的计划,天然产品发现的基础上a)一个新的生物来源的形式洞穴衍生的微生物和B)一个新的分析方法的基础上离子迁移质谱(IM-MS)。这两个方面将为发现天然产物开辟一个新的生物多样性宝库,并提供一种新的方法来加速发现粗提物中的化合物,减少分离过程中的劳动。劳动力和时间的节省来自于基于其IM-MS测量的特性对用于分离和结构解析的代谢物进行优先排序的能力。 目标1.开发使用离子迁移质谱(IM-MS)的天然产物分析。顶-MS是二维质谱法的一种形式,其绘制质/荷比和气相碰撞横截面积,这可能与分子构象和功能性直接相关。我们将评估质量碰撞面积比与天然产物类别的相关性,并将这些相关性与计算预测值进行比较。这些数据将化合物结构、类别和构象映射到IM-MS值。 目标二。开发洞穴微生物作为天然产品多样性的新来源。可培养的地下粘细菌和放线菌的分离、低温保存和基因分类学研究将为天然产物的发现提供新的资源库,并为后续的目标提供提取物的来源。 目标3。开发IM-MS作为一种方法来识别提取物中的候选物。将通过IM-MS评价分类学上独特的生物体的亚组的次级代谢潜力。具有区分化合物类别、功能或独特构象的IM-MS特性的化合物将用于分离/结构解析。 这些目标是平行的,但是协同的。从复杂来源中鉴定次级代谢物的新方法对于加速发现至关重要。不断需要新的生物多样性来源,以扩大获得其生物合成分子多样性的机会。洞穴微生物将提供开发IM-MS所需的提取物的生物来源,作为鉴定提取物中次级代谢产物的工具。通过提出的方法发现的天然产物将可用于NIH分子库计划(MLP),包括分子库探针生产中心网络(MLPCN)、分子库小分子库(MLSMR)和PubChem。
公共卫生关系:天然产物是药物的极好来源,但它们很难被发现,因为它们必须被鉴定为来自生物来源的复杂提取物的次要组分。我们建议开发二维分离的分子结构和质量的基础上,以指导复杂的生物来源的天然产物的鉴定。此外,将调查洞穴微生物,这是以前未开发的生物多样性来源,以发现天然产品。
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)
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BRIAN O BACHMANN其他文献
BRIAN O BACHMANN的其他文献
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$ 36.93万 - 项目类别:
New Methodologies for Accelerating Natural Product Discovery
加速天然产品发现的新方法
- 批准号:
8272698 - 财政年份:2010
- 资助金额:
$ 36.93万 - 项目类别:
New Methodologies for Accelerating Natural Product Discovery
加速天然产品发现的新方法
- 批准号:
7845955 - 财政年份:2010
- 资助金额:
$ 36.93万 - 项目类别:
New Methodologies for Accelerating Natural Product Discovery
加速天然产品发现的新方法
- 批准号:
9013482 - 财政年份:2010
- 资助金额:
$ 36.93万 - 项目类别:
New Methodologies for Accelerating Natural Product Discovery
加速天然产品发现的新方法
- 批准号:
8888885 - 财政年份:2010
- 资助金额:
$ 36.93万 - 项目类别:
New Methodologies for Accelerating Natural Product Discovery
加速天然产品发现的新方法
- 批准号:
9421557 - 财政年份:2010
- 资助金额:
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