Exploring microbial biosynthetic pathways

探索微生物生物合成途径

• 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: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=738575
• 关键词: Exploring; microbial; biosynthetic; pathways

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.

微生物会产生一系列令人震惊的不同化学物质，其中包括一类不寻常的分子，它们具有一种名为磷酸盐的碳-磷(C-P)键。虽然一些(如抗生素磷霉素)已经被深入研究并取得了商业上的成功，但磷酸盐仍然是一类被忽视的天然分子。更未被探索的是细胞表面的自然发生的磷酸盐修饰。尽管预测在自然界中广泛存在，但令人惊讶的是，这些修饰几乎没有被描述出来，而且几乎不知道它们的生物学作用。在化学上，磷酸盐的氧化程度较低，比其在所有生物体中主导中心代谢的磷酸盐更具抗水解性。对于微生物来说，这意味着可能在低氧环境中或在逃避宿主溶酶体防御方面发挥作用。这项研究计划系统地识别和表征磷酸盐的修饰，并了解它们是如何在细菌细胞中制造的。除了揭示细胞表面磷酸盐是如何制造的以及它们在做什么之外，我们的目标是利用这些催化活性来开发制造改性生物材料的可持续技术。具体地说，使用酶生物催化剂来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路线中所需的重金属。除了更低的能量投入和更少的有毒废物，这些无污染的产品还符合生物医学应用的高标准。