郑裕国院士团队汤晓玲、柳志强教授实现L-蛋氨酸高效生物合成

Core Viewpoint - The article discusses the innovative research on L-methionine synthesis through engineered enzymes, highlighting advancements in enzyme stability and activity, which are crucial for industrial applications in various sectors such as feed, pharmaceuticals, and food [3][4][10]. Group 1: Enzyme Engineering and Research Findings - L-methionine is an essential amino acid with significant applications in feed, pharmaceuticals, and food industries, making its efficient biosynthesis a research focus in biotechnology [3]. - The research team developed a fermentation-enzyme synthesis route for L-methionine, utilizing a high-efficiency cell factory to produce the precursor O-succinyl-L-homoserine (OSH) [3][4]. - A novel strategy called "dynamic network rigidification-local flexibility regulation" was proposed to enhance enzyme activity and stability, addressing the long-standing "activity-stability trade-off" in protein engineering [3][4]. Group 2: Key Experimental Results - The study identified 20 potential mutation sites in the enzyme O-succinyl-L-homoserine mercaptotransferase (CvMetZ) through consensus sequence analysis, leading to beneficial mutations such as T59I and A241T, which improved half-life and enzyme activity significantly [4][5]. - The half-life of the T59I mutant increased from 3.3 hours to 9.8 hours, with a 28% increase in enzyme activity, while A241T achieved a half-life of 11.2 hours and a 25% activity increase [4][9]. - The combination of multiple mutations resulted in a triple mutant (T59I/T119Y/A241T) that exhibited a half-life of 20.6 hours and a 36% increase in enzyme activity, demonstrating the effectiveness of the engineered design [8][9]. Group 3: Industrial Application and Cost Efficiency - The modified enzymes were subjected to immobilization studies, achieving high immobilization efficiency and activity recovery, with over 90% activity retained after the first 10 batches and over 60% after 30 batches [10]. - The fermentation enzyme method for L-methionine synthesis demonstrated a yield of 92.8% using over 100 g/L of O-succinyl-L-homoserine as a substrate, providing critical data for large-scale production [10].