膦酸类化合物是指分子结构中含有碳磷键的化合物，在结构已知的十数种膦酸类小分子天然产物中开发成药的就有两个，磷霉素（抗感染）和双丙氨膦（除草剂）。膦酸类天然产物中碳磷键的生物合成机制迄今为止知道的只有一种，即磷酸烯醇式丙酮酸变位酶催化的磷酸烯醇式丙酮酸分子内重排反应。K-26是放线菌产生的一个膦酸三肽小分子化合物，已有的同位素标记的前体物喂养实验表明K-26的碳磷键不是通过这种已知的生物化学反应合成的。它的碳原子来源于酪氨酸，磷原子来源于什么前体物尚不知道。本研究将克隆K-26的生物合成基因簇，阐明K-26的生物合成途径，揭示一种崭新的碳磷键生物合成酶学机制。

Phosphonates (Phns) refer to a group of compounds containing carbon-phosphorus (C-P) bond in chemical structures. Around a dozen of naturally occurring small molecule Phns have been identified and two of them have been successfully developed as drugs.For example,Fosfomycin has been clinically used as anti-infection agent and Phosphinothricin tripeptide has been agriculturally used as herbicide. However, only one enzymological mechanism, phosphoenolpyruvate (PEP) inter-molecular rearrangement reation catalyzed by PEP mutase, has been recognized for the biosynthesis of the Phns C-P bond. Phns tripeptide K-26 is produced by certain Actinomyces strains and its C-P bond biosynthesis mechanism has been shown to be different from the known mechanism through an isotope labeled precursor feeding experiment. The carbon of K-26 C-P bond originates from tyrosine while the origin of phosphorus remains obscure. In this project, we will characterize K-26 biosynthesis gene cluster and its biosynthesis pathway. It will reveal a brand new enzymological mechanism for the biosynthesis of the C-P bond.