Genomic approaches of discovery broad-spectrum antimicrobial agents
发现广谱抗菌药物的基因组方法
基本信息
- 批准号:7669772
- 负责人:
- 金额:$ 34.21万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-03-25 至 2014-02-28
- 项目状态:已结题
- 来源:
- 关键词:Actinobacteria classActinomycesActinomycetalesAntibioticsBacteriaBioinformaticsBiological FactorsChemistryCulture MediaEcologyElementsEnvironmentFundingGene ClusterGeneticGenomeGenomicsGoalsGrantInstitutesMethodologyMicrobeNational Institute of Allergy and Infectious DiseaseNew EnglandNutrientPilot ProjectsProductionResistanceScreening procedureSimulateantimicrobialantimicrobial drugbasebiodefensecombatmicrobialnovelpathogenprogramspromoterscaffoldsmall moleculetool
项目摘要
Most clinically-used antibiotics are bacterially-produced small molecules known as natural products, or their
derivatives. However, natural products are not being featured in antibiotic discovery programs due to high
rates of rediscovery and low rates of new molecule discovery. This proposal describes a new genomicsbased
approach to natural product discovery that employs a combination of bioinformatics, microbial
ecology, genetics, and chemistry to identify cryptic biosynthetic loci and stimulate them to produce their
encoded natural products. All molecules identified will be characterized for antimicrobial activity.
Specific Aim 1. Use bioinformatics to identify biosynthetic gene clusters and predict their products. New
bioinformatic tools will be developed to identify biosynthetic gene clusters in the genomes of actinomycetes
and other microbes, and to predict structural elements of their small molecule products. These predictions
will be leveraged toward antibiotic discovery by using them as the basis for efforts to stimulate the production
of cryptic natural products, as described in Specific Aims 2 and 3:
Specific Aim 2. Stimulate the production of cryptic metabolites by simulating a multispecies environment.
Most screens for new natural products have been performed with strains grown as pure cultures in nutrientrich
growth media. A new screening format has recently been developed in which strains are grown as
microcolonies on nutrient-poor growth media. This microcolony screening methodology will be used to
identify cryptic natural products with antimicrobial activity.
Specific Aim 3. Stimulate the production of cryptic metabolites by genetically manipulating producers. Most
natural product-encoding gene clusters are thought to be repressed under standard culture conditions.
Using actinomycete strains whose biosynthetic gene clusters have been identified by the efforts described in
Specific Aim 1, endogenous gene cluster promoters will be systematically replaced with a strong, inducible
promoter, enabling the controlled synthesis and isolation of their small molecule products and the
subsequent characterization of their antimicrobial activity. .
大多数临床使用的抗生素是细菌产生的小分子,称为天然产物,或其
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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Jon Clardy的其他文献
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{{ truncateString('Jon Clardy', 18)}}的其他基金
Identification and characterization of gut microbial bioactive molecules that determine predisposition to autoimmune disease and atopy
确定自身免疫性疾病和特应性倾向的肠道微生物生物活性分子的鉴定和表征
- 批准号:
10239455 - 财政年份:2017
- 资助金额:
$ 34.21万 - 项目类别:
Identification and characterization of gut microbial bioactive molecules that determine predisposition to autoimmune disease and atopy
确定自身免疫性疾病和特应性倾向的肠道微生物生物活性分子的鉴定和表征
- 批准号:
9238030 - 财政年份:2017
- 资助金额:
$ 34.21万 - 项目类别:
Identification and characterization of gut microbial bioactive molecules that determine predisposition to autoimmune disease and atopy
确定自身免疫性疾病和特应性倾向的肠道微生物生物活性分子的鉴定和表征
- 批准号:
9889899 - 财政年份:2017
- 资助金额:
$ 34.21万 - 项目类别:
Novel therapeutic agents from the bacterial symbionts of Brazilian invertebrates
来自巴西无脊椎动物细菌共生体的新型治疗剂
- 批准号:
8902965 - 财政年份:2014
- 资助金额:
$ 34.21万 - 项目类别:
Novel therapeutic agents from the bacterial symbionts of Brazilian invertebrates
来自巴西无脊椎动物细菌共生体的新型治疗剂
- 批准号:
9335718 - 财政年份:2014
- 资助金额:
$ 34.21万 - 项目类别:
Novel therapeutic agents from the bacterial symbionts of Brazilian invertebrates
来自巴西无脊椎动物细菌共生体的新型治疗剂
- 批准号:
8785542 - 财政年份:2014
- 资助金额:
$ 34.21万 - 项目类别:
Genomic approaches of discovery broad-spectrum antimicrobial agents
发现广谱抗菌药物的基因组方法
- 批准号:
8233437 - 财政年份:2011
- 资助金额:
$ 34.21万 - 项目类别:
STRUCTURAL AND MECHANISTIC STUDIES OF THE PANTOCIN A BIOSYNTHESIS
全解菌素A生物合成的结构和机理研究
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7955137 - 财政年份:2009
- 资助金额:
$ 34.21万 - 项目类别:
Molecule-to-gene approaches to new natural products
新天然产物的分子到基因方法
- 批准号:
7559105 - 财政年份:2008
- 资助金额:
$ 34.21万 - 项目类别:
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