膦酸类化合物是指分子结构中含有碳磷键的化合物，膦酸类天然产物在自然界中广泛存在，但是已经鉴定结构的膦酸小分子天然产物并不多。膦酸小分子天然产物大多具有良好的生物学活性，已知的十数个化合物中就有两个被开发成药：磷霉素（抗感染药物）和草胺膦（除草剂）。膦酸类天然产物碳磷键的生物合成非常有规律，至今所知它们都是由磷酸烯醇式丙酮酸变位酶（PEP Mutase）催化的PEP分子内重排反应生成的。膦酸类化合物的碳磷键具有非常强的仪器检测特异性，核磁共振仪检测时膦酸类化合物的31P化学位移大于10 ppm，而磷酸酯类化合物的31P化学位移小于5 ppm；质谱仪检测时膦酸类化合物断裂产生的PO2-子离子比H2PO4-子离子多，而磷酸酯类化合物断裂产生的PO2-子离子比H2PO4-子离子少。据此，本项目将先进行基因筛选然后通过仪器筛选，发掘新的膦酸小分子天然产物，并鉴定其化学结构、解析其生物合成途径。

Phosphonates (Phns) are a group of compounds containing carbon-phosphorus (C-P) bond in chemical structures. Naturally occurring Phns are widely spread and more than a dozen of naturally occurring small molecule Phns (NOSMPs) have been identified. These NOSMPs showed excellent bioactivity against a wide range of targets.For example,Fosfomycin is clinically used as an anti-infection agent and Phosphinothricin tripeptide is agriculturally used as a herbicide. It has been shown that the mechnism of naturally occurring C-P bond biosynthesis is highly conserved.All C-P bonds are generated from a phosphoenolpyruvate (PEP) intermolecular rearrangement reaction catalyzed by PEP mutase which is encoded by pepM gene.Moreover, the readout of Phns C-P bond from both mass spectrometer (MS) and nuclear magnetic resonance spectrometer (NMR) are specific. For instance, the NMR 31P chemical shift of Phns is more than 10 ppm, while the shift of phosphates is less than 5 ppm. When analyzed by MS, fragmentation of Phns generates more PO2- daughter ions, while phosphates produce more H2PO4- daughter ions. Therefore, we propose to develop a novel method of NOSMPs identification using both pepM gene screening and NMR/MS screening. The long term goal is to characterize chemical structures as well as biosynthesis pathways of these newly identified Phns.