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.

项目摘要由稳定的碳磷（C-P）键的存在定义的磷酸是一种不足具有巨大生物医学承诺的化合物组，源于（1）临床和商业应用，（2）细胞目标和作用方式的巨大多样性（3）允许轻松发现和表征的一系列研究工具，（4）新颖的，未经char-的库存班级的定期成员，以及（5）不寻常的生物合成途径，其表征增强了并扩展了我们对基本生物化学的了解。该研究项目利用了这些FEA- Tures，专注于具有有用的生物活性和有趣化学特征的磷酸天然产品，如以及新型磷酸盐的发现。该项目的长期目标包括阐明基因，选定磷酸盐的生物合成途径，耐药机制和生物活性，以及特征涉及其合成的新型酶活性的构造。拟议资金的具体目的周期为：（1）表征磷刺蛋白和相关分子的生物合成和生物活性的表征，（2）表征由宿主相关的肠oc-产生的膦酸酯的生物合成和生物活性的表征 Teria和（3）开发了改进的磷酸基因组开采工具。关联这项研究有可能发现具有有用的生物活性和有趣的磷酸天然产物化学特征。此外，对基因，酶和生物合成途径的表征这些化合物的产生可能揭示了新颖的生物化学，这大大扩展了我们的理解微生物催化的化学转化，同时为产生过度的菌株铺平了道路杜切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 Novel Biosynthetic Gene Cluster Across the Pantoea Species Complex Is Important for Pathogenicity in Onion.