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Discovery, biosynthesis and bioactivity of phosphonic acid natural products

膦酸天然产物的发现、生物合成及生物活性

基本信息

批准号：
10586384
负责人：
WILLIAM W METCALF
金额：
$ 37.16万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-01 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10586384
关键词：
Address Anabolism Anti-Bacterial Agents Antibiotics Antihypertensive Agents Antimalarials Atlases Bacteria Bacterial Infections Biochemical Biochemistry Bioinformatics Biological Carbon Categories Chemicals Classification Clinical Collaborations Collection Data Development Enterobacteriaceae Enzymatic Biochemistry Enzyme Inhibition Enzymes Erwinia Escherichia coli Family Funding Gene Cluster Genes Genetic Genome Goals Grouping Growth In Vitro Investigation Knowledge Medical Medicine Metabolic Microbe Mining Molecular Natural Products Osteoporosis Output Pathway interactions Phosphinic Acids Phosphonic Acids Phosphorus Production Property Proteins Publishing Research Research Project Grants Riboflavin Role Source Testing Universities Virus Diseases bioactive natural products biosynthetic product cellular targeting clinical application commercial application fungus gene product host-associated microbial communities host-microbe interactions improved in vivo inhibitor inorganic phosphate insight member microbial novel phosphonate programs resistance gene resistance mechanism small molecule stem tool

项目摘要

Project Summary Phosphonic acids, defined by the presence of stable carbon-phosphorus (C-P) bonds, are an underexploited group of compounds with great biomedical promise, which stems from (1) a proven track record in clinical and commercial applications, (2) an immense diversity of cellular targets and modes of action (3) availability of a suite of research tools that allow facile discovery and characterization, (4) a proven reservoir of novel, unchar- acterized members of the class, and (5) unusual biosynthetic pathways whose characterization has enhanced and expanded our knowledge of fundamental biochemistry. This research project takes advantage of these fea- tures, focusing on phosphonate natural products with useful bioactivities and interesting chemical features, as well as the discovery of novel phosphonates. The long-term goals of the project include elucidation of the genes, biosynthetic pathways, resistance mechanisms and bioactivities of selected phosphonates, as well as charac- terization of novel enzymatic activities involved in their synthesis. The specific aims for the proposed funding period are: (1) characterization of the biosynthesis and bioactivity of phosphonothrixin and related molecules, (2) characterization of the biosynthesis and bioactivity of phosphonates produced by host-associated enterobac- teria, and (3) development of improved genome-mining tools for phosphonate discovery. Relevance This research has the potential to discover phosphonate natural products with useful bioactivities and interesting chemical features. Moreover, characterization of the genes, enzymes and biosynthetic pathways needed for production of these compounds is likely to reveal novel biochemistry that significantly expands our understanding of the chemical transformations catalyzed by microbes, while paving the way for creation of strains that overpro- duce useful molecules and their derivatives.

项目摘要膦酸，由稳定的碳-磷（C-P）键的存在定义，是一种开发不足的一组具有巨大生物医学前景的化合物，这源于（1）在临床和商业应用，（2）细胞靶点和作用模式的巨大多样性，（3）一套研究工具，允许容易发现和表征，（4）一个证明了新的，不加修饰的，（5）不寻常的生物合成途径，其特征已增强并扩展了我们的基础生物化学知识。该研究项目利用这些fea- tures，重点是具有有用的生物活性和有趣的化学特征的膦酸盐天然产物，以及新膦酸盐的发现。该项目的长期目标包括阐明基因，生物合成途径，抗性机制和选定的膦酸盐的生物活性，以及charac，涉及其合成的新酶活性的化。拟议供资的具体目标阶段是：（1）膦酰三辛和相关分子的生物合成和生物活性的表征， (2)表征宿主相关肠杆菌产生的膦酸酯的生物合成和生物活性， teria，和（3）改进的膦酸盐发现的基因组挖掘工具的开发。相关性这项研究有可能发现具有有用的生物活性和有趣的膦酸酯天然产物化学特征此外，表征基因，酶和生物合成途径所需的这些化合物的生产可能揭示新的生物化学，大大扩展了我们的理解微生物催化的化学转化，同时为创造过度增殖的菌株铺平了道路，产生有用的分子及其衍生物。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

antiSMASH 7.0: new and improved predictions for detection, regulation, chemical structures and visualisation.

DOI：
10.1093/nar/gkad344
发表时间：
2023-07-05
期刊：
NUCLEIC ACIDS RESEARCH
影响因子：
14.9
作者：
Blin, Kai;Shaw, Simon;Augustijn, Hannah E.;Reitz, Zachary L.;Biermann, Friederike;Alanjary, Mohammad;Fetter, Artem;Terlouw, Barbara R.;Metcalf, William W.;Helfrich, Eric J. N.;van Wezel, Gilles P.;Medema, Marnix H.;Weber, Tilmann
通讯作者：
Weber, Tilmann

A Phosphonate Natural Product Made by Pantoea ananatis is Necessary and Sufficient for the Hallmark Lesions of Onion Center Rot.

由Pantoea ananatis生产的膦酸酯天然产物对于洋葱中心腐病的标志性病变是必需的且足够的。