草铵膦的应用、生物合成与降解

Application,biosynthesis and degradation of phosphinothricin

传统的非选择性除草剂市场近十几年来发生了剧烈的变化,比如百草枯由于其较高的毒性和致死率逐渐被多个国家禁用,草甘膦由于抗性的累积以及对环境造成的负担市值逐渐降低,草铵膦(phosphinothricin,PT)作为后起之秀市场占比正在稳步增加。草铵膦是20世纪70年代发现的一种次膦酸化合物,可以与谷氨酰胺合成酶结合,不可逆地抑制其活性,从而杀灭杂草。以草铵膦为药效核心的天然产物双丙氨膦生物合成途径中存在许多不寻常的生化反应:首先,大多数非核糖体肽合成酶会选择含有未修饰的α-氨基的底物,而双丙氨膦合成途径中的非核糖体肽合成酶选择了α-氨基被乙酰化修饰的底物;其次,草铵膦结构中独特的C-P-C(碳-磷-碳)键结构单元的生物合成涉及到的P-甲基转移酶既是研究的热点,也是研究的难点。另一方面,作为一种天然产物,草铵膦在生物降解方面具有得天独厚的优势。虽然目前对草铵膦具体的生物降解途径所知甚少,但从其它的膦酸天然产物生物降解的研究中我们可以得到很多有益的启示。本文将从草铵膦的应用、生物合成、生物降解3个方面展开,对草铵膦的研究现状进行综述。

The traditional non-selective herbicide market has experienced dramatic changes.For example,paraquat has been gradually banned in many countries for its high toxicity and lethality;the market value of glyphosate is decreasing due to the accumulation of resistance and the burden on the environment;the market share of phosphinothricin is increasing steadily as a rising star.Phosphinothricin is a kind of phosphinic acid compound found in 1970s,which can irreversibly bind glutamine synthetase,inhibit its activity,and accordingly kill weeds.Many interesting reactions happened in the biosynthesis of bialaphos,a nature product with phosphinothricin as the pharmacophore.The majority of nonribosomal peptide synthetases prefer substrates with a freeα-amino group,while the nonribosomal peptide synthetase involved in bialaphos biosynthesis takes the N-acetylated one.Characterization of P-methyl transferase responsible for the synthesis of unique C-P-C moiety is not only a research hotspot,but also a grand challenge.Meanwhile,as a natural product,phophinothricin has showed unique advantages in biodegradation.Although the exact biodegradation pathway of phosphinothricin remains unclear,many useful insights can be drawn out from studies on the biodegradation of other phosphonic acid natural products.In this article,the topic will focus on three aspects of phosphinothricin:Application,biosynthesis,and biodegradation.