Harnessing the biosynthetic potential of bacteria to produce ribosomally synthesised natural products
利用细菌的生物合成潜力生产核糖体合成的天然产物
基本信息
- 批准号:BB/V016024/1
- 负责人:
- 金额:$ 70.71万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Research Grant
- 财政年份:2021
- 资助国家:英国
- 起止时间:2021 至 无数据
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Bacteria make an incredible number of chemical compounds that are invaluable for a variety of medical and agricultural purposes, including antibiotics, antifungals, anticancer compounds and insecticides. In fact, the majority of clinically used antibiotics come from soil-dwelling bacteria. This ability to produce these biologically active natural products stems from the evolutionary advantage the molecules provide to the producer. For example, bacteria have evolved the ability to produce powerful antibiotics to kill competing neighbouring microbes. The recent crisis in the rise of multi-drug resistant bacterial infections means that there is a pressing need to discover new antibiotics. We believe that there are many novel antibiotics that remain to be discovered from bacteria, but existing discovery methods are missing many hidden molecules that we call "metabolic dark matter".These natural products are produced by the action of a series of enzymes (proteins), which are encoded by genes (DNA) in the bacterial genome. Hundreds of thousands of bacterial genomes have now been sequenced. Researchers have developed methods to predict what compounds a bacterium should be able to make based on this genomic data ("genome mining"). This has revealed that many bacteria appear to be capable of producing many more compounds than have been identified. These cryptic compounds may be potent medicines or have other important biological functions. This makes the identification of these pathways and the associated compounds an important research goal. However, we hypothesise that many important pathways are missed by existing genome mining methods. In this project, we will use a combination of computational, genetic and chemical methods to identify these molecules, understand how they are made and analyse them for biological activity towards clinically and agriculturally important pathogens. We will focus on discovering new members of a class of natural product called ribosomally synthesised and post-translationally modified peptides (RiPPs). These are made across nature, from bacteria to monkeys, using the same biological machinery that makes large proteins. However, RiPP pathways have evolved to make much smaller natural products that have potent bioactivity. RiPPs include thiostrepton, which is used as an antibiotic to treat bacterial infections in veterinary medicine, nisin, a peptide with broad spectrum antibacterial activity that is used in food processing to suppress bacterial growth, and ziconotide, which is derived from a cone snail RiPP and is used to treat chronic pain in humans.
细菌产生大量的化合物,这些化合物对于各种医疗和农业用途都是非常宝贵的,包括抗生素,抗真菌剂,抗癌化合物和杀虫剂。事实上,大多数临床使用的抗生素来自土壤细菌。这种产生这些生物活性天然产物的能力源于分子为生产者提供的进化优势。例如,细菌已经进化出产生强大抗生素的能力,以杀死邻近的竞争微生物。最近多重耐药细菌感染的危机意味着迫切需要发现新的抗生素。我们认为,还有许多新的抗生素有待从细菌中发现,但现有的发现方法遗漏了许多隐藏的分子,我们称之为“代谢暗物质”,这些天然产物是由一系列酶(蛋白质)的作用产生的,这些酶由细菌基因组中的基因(DNA)编码。现在已经对数十万种细菌的基因组进行了测序。研究人员已经开发出基于这些基因组数据预测细菌应该能够制造什么化合物的方法(“基因组挖掘”)。这表明,许多细菌似乎能够产生比已经确定的更多的化合物。这些隐藏的化合物可能是有效的药物或具有其他重要的生物学功能。这使得这些途径和相关化合物的鉴定成为一个重要的研究目标。然而,我们假设现有的基因组挖掘方法错过了许多重要的途径。在这个项目中,我们将使用计算,遗传和化学方法的组合来识别这些分子,了解它们是如何制造的,并分析它们对临床和农业重要病原体的生物活性。我们将专注于发现一类称为核糖体合成和后修饰肽(RIPPs)的天然产物的新成员。从细菌到猴子,这些蛋白质都是由自然界中的生物制造的,使用的是制造大型蛋白质的相同生物机制。然而,RiPP途径已经发展成具有有效生物活性的小得多的天然产物。RiPP包括硫链丝菌素,其在兽医学中用作治疗细菌感染的抗生素;乳链菌肽,其是具有广谱抗菌活性的肽,其用于食品加工以抑制细菌生长;以及齐考诺肽,其源自锥形蜗牛RiPP并用于治疗人类的慢性疼痛。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Beyond Soil-Dwelling Actinobacteria: Fantastic Antibiotics and Where to Find Them.
- DOI:10.3390/antibiotics11020195
- 发表时间:2022-02-02
- 期刊:
- 影响因子:0
- 作者:Santos-Aberturas J;Vior NM
- 通讯作者:Vior NM
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Andrew Truman其他文献
PD46-11 PHOSPHORYLATION AND UBIQUITINATION REGULATE PROTEIN PHOSPHATASE-5 ACTIVITY AND ITS PROSURVIVAL ROLE IN KIDNEY CANCER
- DOI:
10.1016/j.juro.2018.02.2159 - 发表时间:
2018-04-01 - 期刊:
- 影响因子:
- 作者:
Natela Dushukyan;Michael Daneshvar;Rebecca Sager;Mark Woodford;Alexander Baker-Williams;John Chisholm;David Loiselle;Andrew Truman;Timothy Haystead;Oleg Shapiro;Dimitra Bourboulia;Gennady Bratslavsky;Mehdi Mollapour - 通讯作者:
Mehdi Mollapour
Andrew Truman的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Andrew Truman', 18)}}的其他基金
Extending bicyclomycin treatment of multi-drug resistant Gram-negative pathogens
延长双环霉素对多重耐药革兰氏阴性病原体的治疗
- 批准号:
MR/P007570/1 - 财政年份:2016
- 资助金额:
$ 70.71万 - 项目类别:
Research Grant
Elucidating and engineering bottromycin biosynthesis
底霉素生物合成的阐明和工程设计
- 批准号:
BB/M003140/1 - 财政年份:2015
- 资助金额:
$ 70.71万 - 项目类别:
Research Grant
相似海外基金
Harnessing the biosynthetic potential of bacteria to produce ribosomally synthesised natural products
利用细菌的生物合成潜力生产核糖体合成的天然产物
- 批准号:
BB/V016059/1 - 财政年份:2021
- 资助金额:
$ 70.71万 - 项目类别:
Research Grant
Harnessing plant biosynthetic pathways to explore novel chemical space in a class of compounds with significant pharmaceutical potential
利用植物生物合成途径探索一类具有重大药物潜力的化合物的新化学空间
- 批准号:
BB/T01010X/1 - 财政年份:2019
- 资助金额:
$ 70.71万 - 项目类别:
Research Grant
Unravelling fungal biosynthetic potential by heterologous expression of silent gene clusters in Aspergillus nidulans and LC-MS-based metabolomic analysis
通过构巢曲霉中沉默基因簇的异源表达和基于 LC-MS 的代谢组学分析揭示真菌生物合成潜力
- 批准号:
410588509 - 财政年份:2019
- 资助金额:
$ 70.71万 - 项目类别:
Research Grants
Understanding carbazole biosynthetic enzymes: potential for a versatile assay of acyl CoAs
了解咔唑生物合成酶:酰基 CoAs 多功能测定的潜力
- 批准号:
BB/R00479X/1 - 财政年份:2018
- 资助金额:
$ 70.71万 - 项目类别:
Research Grant
The hidden secondary metabolite biosynthetic potential of fungi
真菌隐藏的次生代谢物生物合成潜力
- 批准号:
FT160100233 - 财政年份:2017
- 资助金额:
$ 70.71万 - 项目类别:
ARC Future Fellowships
Biosynthetic and toxic potential of ergot: Biological activity of ergot alkaloids and genome mining for the identification further potential toxic secondary metabolites
麦角的生物合成和毒性潜力:麦角生物碱的生物活性和基因组挖掘,用于鉴定进一步潜在的有毒次生代谢物
- 批准号:
227350539 - 财政年份:2012
- 资助金额:
$ 70.71万 - 项目类别:
Research Grants
Molecular anlaysis of microbial enzymes with biodegrative and biosynthetic potential
具有生物降解和生物合成潜力的微生物酶的分子分析
- 批准号:
298316-2009 - 财政年份:2009
- 资助金额:
$ 70.71万 - 项目类别:
Discovery Grants Program - Individual
MECHANISMS OF BIOSYNTHETIC FORMATION OF DEOXY SUGARS
脱氧糖的生物合成形成机制
- 批准号:
2178128 - 财政年份:1986
- 资助金额:
$ 70.71万 - 项目类别: