Exploring microbial biosynthetic pathways

微生物产生了一系列惊人的不同化学物质，包括一类不寻常的具有碳-磷键的分子，称为磷酸盐。尽管一些（如抗生素磷霉素）已被深入研究并取得了商业上的成功，磷酸盐仍然是一类被忽视的天然分子。更未被开发的是自然发生的细胞表面的磷酸盐修饰。尽管被预测在自然界中广泛存在，但令人吃惊的是，这些修饰几乎没有被描述出来，而且对它们的生物学作用几乎一无所知。在化学上，磷酸盐比它们在所有生物体中主导中心代谢的表亲磷酸盐更少被氧化，更耐水解裂解。对于微生物来说，这意味着在低氧环境中或逃避宿主溶酶体防御的可能作用。该研究计划系统地识别和表征膦酸盐修饰，并了解它们是如何在细菌细胞中制造的。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，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。具体来说，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所需的重金属。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。

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.