Cen Yu-Ke, Wang Qi, Gong Huo, Xue Ya-Ping, Zheng Yu-Guo
Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China.
Engineering Research Center of Bioconversion and Biopurification of Ministry of Education, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China.
Biotechnol Lett. 2022 Apr;44(4):561-570. doi: 10.1007/s10529-022-03239-w. Epub 2022 Mar 3.
With the ban of highly toxic herbicides, such as paraquat and glyphosate, phosphinothricin (PPT) is becoming the most popular broad-spectrum and highly effective herbicide. The current PPT products in the market are usually a racemic mixture with two configurations, the D-type and L-type, of which only the L-PPT has the herbicidal activity. The racemic product is not atom economic, more toxic and may cause soil damage. Asymmetric synthesis of L-PPT has become a research focus in recent years, while biological synthesis methods are preferred for its character of environmental friendly and requiring less reaction steps when being compared to the chemical methods. We have developed a biological synthesis route to produce optically pure L-PPT from D,L-PPT in two steps using 2-carbonyl-4- (hydroxymethyl phosphonyl) butyric acid as the intermediate. In this study, we expressed the glutamate dehydrogenase and glucose dehydrogenase using Pichia pastoris as the first time. After a series of optimization, the total L-PPT yield reached 84%. The developed synthesis system showed a high potential for future industrial application. Compare to the previous plasmid-carrying-E. coli expression system, the established method may avoid antibiotic usage and provided an alternative way for industrial synthesis of optically pure L-PPT.
随着百草枯和草甘膦等高毒性除草剂被禁用,草铵膦正成为最受欢迎的广谱高效除草剂。目前市场上的草铵膦产品通常是含有D型和L型两种构型的外消旋混合物,其中只有L-草铵膦具有除草活性。外消旋产品原子经济性差,毒性更大,还可能造成土壤损害。L-草铵膦的不对称合成近年来已成为研究热点,而生物合成方法因其环境友好且与化学方法相比反应步骤较少的特点而更受青睐。我们开发了一条生物合成路线,以2-羰基-4-(羟甲基膦酰基)丁酸为中间体,分两步从D,L-草铵膦制备光学纯的L-草铵膦。在本研究中,我们首次利用毕赤酵母表达谷氨酸脱氢酶和葡萄糖脱氢酶。经过一系列优化,L-草铵膦的总产率达到了84%。所开发的合成系统在未来工业应用中显示出巨大潜力。与之前携带质粒的大肠杆菌表达系统相比,该方法可避免使用抗生素,为光学纯L-草铵膦的工业合成提供了一种替代方法。