Discovery of Antibiotics from Soil Microbiomes Using Metagenomics
利用宏基因组学从土壤微生物组中发现抗生素
基本信息
- 批准号:9906905
- 负责人:
- 金额:$ 67.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-05-01 至 2022-04-30
- 项目状态:已结题
- 来源:
- 关键词:AnabolismAntibioticsBacteriaBacterial Antibiotic ResistanceBase SequenceBiologicalBiological AssayCategoriesClinicalDNA SequenceDrug resistanceEnvironmentGene ClusterGenesGenomeHarvestHigh-Throughput Nucleotide SequencingIndividualInfectionLaboratoriesLaboratory cultureLeadLibrariesMetagenomicsMethodsNatural ProductsPhenotypePlanet EarthProtocols documentationRecording of previous eventsRewardsSamplingSeriesSoilSourceStructureSurfaceTimeUnited StatesWorkbaseclinical developmentclinically relevantcombatcost effectivedesignimprovedinterestmetagenomemicrobiomenovelpathogenic bacteriascreeningsmall molecule
项目摘要
Project summary: Drug-resistant infections kill more than 65,000 people in the United States per year and
the identification of new antibiotics capable of combating antibiotic resistant bacterial pathogens is desperately
needed. Bacterial natural products have a long proven history of being good lead structures for the
development of clinically useful antibiotics but, unfortunately, the discovery of novel natural products from
cultured bacteria has dramatically slowed in recent years. During the same time, the advent of cost effective
high-throughput sequencing and an increasingly sophisticated understanding of bacterial secondary metabolite
biosynthesis have led to two important revelations with respect to the search for new natural products: first,
that the biosynthetic potential of most cultured bacteria, as judged by the number of biosynthetic gene clusters
observed in sequenced genomes, is far greater than previously estimated; second, that the number of bacterial
species in most environments is at least one hundred times greater than the number of species that is readily
cultured. These observations indicate that conventional natural product screening approaches, which rely on
laboratory culturing of random bacterial strains from the environment, have not come close to realizing the full
biosynthetic potential of the earth's microbiome and that a fundamental change in the approach to bacterial
natural products discovery is therefore needed. Consequently, my laboratory has sought to develop methods
to allow natural product discovery from environmental samples, without the need for strain isolation and
cultivation. The approaches I propose to use to harvest small molecules from metagenomic libraries are
divided into two general categories: 1) Sequence-based metagenomics, which relies on DNA sequence
similarity to identify clones containing a specific gene of interest and 2) Function-based metagenomics, which
relies on the random, unbiased screening of individual eDNA clones in phenotypic assays to identify clones
producing bioactive metabolites. Using sequence-based approaches we can interrogate metagenomes for
novel gene clusters (i.e., new antibiotics), as well as clusters that encode congeners of clinically relevant
natural product (i.e., improve the utility of clinically important classes of antibiotics). Our functional screening
studies will focus on developing methods for creating metagenomic libraries that are enriched in natural
product gene clusters to facilitate more efficient screening for novel antibiotics. For this proposal, we will use
our existing pipelines and improved protocols, as they come on-line, to identify novel natural products with
improved activities against antibiotic resistant bacterial pathogens. We have undoubtedly just begun to scratch
the surface of what lies hidden in the genomes of environmental bacteria. The work here will greatly increase
access to the natural products that remain hidden in the environment and ultimately yield a series of novel
natural antibiotics with the potential to better treat antibiotic resistant bacterial pathogens.
!
项目总结:美国每年有超过65000人死于耐药性感染
项目成果
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{{ truncateString('SEAN F BRADY', 18)}}的其他基金
Discovery and characterization of synthetic bioinformatic natural product anticancer agents
合成生物信息天然产物抗癌剂的发现和表征
- 批准号:
10639302 - 财政年份:2023
- 资助金额:
$ 67.8万 - 项目类别:
Synthetic environmental peptide libraries as a source of novel antibiotics
合成环境肽库作为新型抗生素的来源
- 批准号:
10394993 - 财政年份:2019
- 资助金额:
$ 67.8万 - 项目类别:
Synthetic environmental peptide libraries as a source of novel antibiotics
合成环境肽库作为新型抗生素的来源
- 批准号:
10613900 - 财政年份:2019
- 资助金额:
$ 67.8万 - 项目类别:
Discovery of GPCR-active natural products and their biosynthetic genes from the human associated bacteria
从人类相关细菌中发现具有 GPCR 活性的天然产物及其生物合成基因
- 批准号:
10229230 - 财政年份:2017
- 资助金额:
$ 67.8万 - 项目类别:
Discovery of Antibiotics from Soil Microbiomes Using Metagenomics
利用宏基因组学从土壤微生物组中发现抗生素
- 批准号:
10552394 - 财政年份:2017
- 资助金额:
$ 67.8万 - 项目类别:
Discovery of GPCR-active natural products and their biosynthetic genes from the human associated bacteria
从人类相关细菌中发现具有 GPCR 活性的天然产物及其生物合成基因
- 批准号:
10198774 - 财政年份:2017
- 资助金额:
$ 67.8万 - 项目类别:
Development and application of a functional metagenomic antibiotic discovery pipeline
功能性宏基因组抗生素发现管道的开发和应用
- 批准号:
8932426 - 财政年份:2015
- 资助金额:
$ 67.8万 - 项目类别:
Development and application of a functional metagenomic antibiotic discovery pipeline
功能性宏基因组抗生素发现管道的开发和应用
- 批准号:
9123633 - 财政年份:2015
- 资助金额:
$ 67.8万 - 项目类别:
A minimally invasive synthetic bio-driven approach for natural products discovery
用于天然产物发现的微创合成生物驱动方法
- 批准号:
9102130 - 财政年份:2015
- 资助金额:
$ 67.8万 - 项目类别:
A minimally invasive synthetic bio-driven approach for natural products discovery
用于天然产物发现的微创合成生物驱动方法
- 批准号:
8867550 - 财政年份:2015
- 资助金额:
$ 67.8万 - 项目类别:
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