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: 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

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.

微生物产生了一系列令人震惊的不同化学物质，包括一类不寻常的具有碳-磷（C-P）键的分子，称为膦酸盐。虽然一些（例如抗生素磷霉素）已被深入研究并取得了商业成功，但膦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天然存在的膦酸盐修饰。虽然预测在自然界中广泛存在，但令人惊讶的是，这些修饰很少被描述，而且几乎对它们的生物学作用一无所知。在化学上，膦酸盐比它们的磷酸盐表亲更少氧化，更耐水解裂解，磷酸盐在所有生物体中占主导地位。对于微生物来说，这意味着可能在低氧环境中或逃避宿主溶酶体防御中发挥作用。该研究计划系统地识别和表征膦酸盐修饰，并了解它们如何在细菌细胞中制造。除了揭示细胞表面膦酸盐是如何产生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用于制造改性生物材料的可持续技术。具体来说，使用酶生物催化剂修饰聚合物材料不需要传统化学合成路线中所需的氯化有机溶剂、极端温度或重金属。除了降低能源投入和减少有毒废物外，无污染产品还符合生物医学应用所需的高标准。