Exploring microbial biosynthetic pathways

探索微生物生物合成途径

基本信息

批准号：
RGPIN-2019-05897
负责人：
Horsman, Geoffrey
金额：
$ 2.62万
依托单位：
Wilfrid Laurier University
依托单位国家：
加拿大
项目类别：
Discovery Grants Program - Individual
财政年份：
2020
资助国家：
加拿大
起止时间：
2020-01-01 至 2021-12-31
项目状态：
已结题

来源：
https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=715266
关键词：
Exploring microbial biosynthetic pathways

项目摘要

Microbes generate an astounding array of diverse chemistry, including an unusual class of molecules possessing a carbon-phosphorus (C-P) bond called phosphonates. Although some (e.g. the antibiotic fosfomycin) have been intensively studied and led to commercial success, phosphonates remain an overlooked class of natural molecules. Even more underexplored are naturally-occurring phosphonate modifications of cell surfaces. Although predicted to be widespread in Nature, startlingly few of these modifications have been characterized, and virtually nothing is known about their biological roles. Chemically, phosphonates are less oxidized and more resistant to hydrolytic cleavage than their phosphate cousins that dominate central metabolism in all organisms. For microbes, this implies possible roles in low oxygen environments or in evading host lysosomal defences. This research program is systematically identifying and characterizing phosphonate modifications and understanding how they are manufactured in the bacterial cell. In addition to revealing how cell surface phosphonates are made and what they are doing, we aim to harness these catalytic activities to develop sustainable technologies for manufacturing modified biomaterials. Specifically, using enzyme biocatalysts to modify polymeric materials does not require chlorinated organic solvents, extreme temperatures, or heavy metals required in traditional chemical synthetic routes. In addition to lower energy input and reduced toxic waste, the contaminant-free products meet high standards required for biomedical applications.

微生物产生了一个惊人的化学阵列，包括具有称为磷酸盐的碳磷（C-P）键的不寻常的分子。尽管有些（例如抗生素fosfomycin）已经深入研究并带来了商业成功，但磷酸盐仍然是一类被忽视的天然分子。更加无流动的是细胞表面的自然磷酸化修饰。尽管预计在本质上是广泛的，但这些修饰中很少有特征，而且几乎对它们的生物学作用一无所知。从化学上讲，磷酸盐的氧化较少，对水解裂解的抗性比其磷酸盐表亲在所有生物体中主导了中央代谢。对于微生物，这意味着在低氧气环境或逃避宿主溶酶体防御方面的可能作用。该研究计划正在系统地识别和表征磷酸盐的修饰，并了解它们在细菌细胞中的生产方式。除了揭示如何制造细胞表面磷酸盐及其在做什么外，我们还旨在利用这些催化活性来开发可持续的技术来制造改良的生物材料。具体而言，使用酶生物催化剂修饰聚合物材料不需要氯化有机溶剂，极端温度或传统化学合成途径中所需的重金属。除了降低能量输入和减少有毒废物外，无污染物的产品符合生物医学应用所需的高标准。