膦酸类天然产物以其良好的药用活性及丰富的化学结构是近年来天然产物领域的研究热点之一。本项目的研究对象膦酸类化合物Argolaphos A 具有较强的和卡那霉素相当的抗菌效果，极具广阔的的临床开发潜力。化学结构上，Argolaphos A显著区别于其它膦酸类天然产物，第一，其前体是氨甲基膦酸， 这是自然界首次发现此类型膦酸类化合物；第二， Argolaphos A中含有一个非天然氨基酸N5-精氨酸, 这种氨基酸在自然界极为少见，暗示该类化合物的生物合成过程中可能蕴含着新型酶催化机制。时至今日，氨甲基膦酸类天然产物的生物合成途径还未有报道，本项目拟从克隆Argolaphos A的生物合成基因簇入手，综合运用分子遗传学、生物化学等手段，在揭示该分子生物合成机制的基础上，建立细菌氨甲基膦酸为前体的化合物的生物合成通路， 并揭示其中新型酶的催化机制。

Phosphonates have been one of the hot topics in the research field of natural products recently due to their excellent pharmaceutical applications as well as their rich structural diversities. Phosphonate antibiotic Argolaphos A, the target compound in this project, exhibits as strong antibacterial activity as kanamycin and has a great potential to be developed into a novel antibiotic in clinic. The chemical structure of Argolaphos A has been characterized by containing both the precursor aminomethylphosphonate (AMP), which distinguishes it from other natural phosphonates and N5-arginine, which is non-natural amino acid and rare in Nature. This finding indicates that a novel enzymatic mechanism may be involved in the biosynthesis of this family of compounds in bacteria. To date, the detailed biosynthetic mechanism for AMP-containing compounds remains elusive. In this context, we will set out to isolate and characterize the biosynthetic gene cluster of Argolaphos A, and to establish a general biosynthesis model for the bacterial AMP-containing compounds and uncover catalytic mechanism of novel enzymes involved in the biosynthesis of Argolaphos A.