Phosphonates are organophosphorus compounds possessing a characteristic C-P bond in which phosphorus is directly bonded to carbon. As phosphonates mimic the phosphates and carboxylates of biological molecules to potentially inhibit metabolic enzymes, they could be lead compounds for the development of a variety of drugs. Fosfomycin (FM) is a representative phosphonate natural product that is widely used as an antibacterial drug. Here, we review the biosynthesis of FM, which includes a recent breakthrough to find a missing link in the biosynthetic pathway that had been a mystery for a quarter-century. In addition, we describe the genome mining of phosphonate natural products using the biosynthetic gene encoding an enzyme that catalyzes C-P bond formation. We also introduce the chemoenzymatic synthesis of phosphonate derivatives. These studies expand the repertoires of phosphonates and the related biosynthetic machinery. This review mainly covers the years 2012-2020.

中文翻译：

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膦酸天然产物生产中涉及的生物合成途径和酶。

膦酸酯是具有特征性CP键的有机磷化合物，其中磷直接键合到碳上。由于膦酸酯模拟生物分子的磷酸盐和羧酸盐可能抑制代谢酶，因此它们可能是开发多种药物的先导化合物。磷霉素（FM）是代表性的膦酸酯天然产物，被广泛用作抗菌药物。在这里，我们回顾了FM的生物合成，其中包括最近的一项突破，即发现生物合成途径中缺失的环节已是25个世纪的谜。此外，我们描述了使用编码催化CP键形成的酶的生物合成基因对膦酸酯天然产物进行基因组挖掘。我们还介绍了膦酸酯衍生物的化学酶法合成。这些研究扩大了膦酸酯的种类和相关的生物合成机制。这项审查主要涵盖2012-2020年。