浙工大柳志强等改造大肠杆菌高产 1,4-丁二醇

Core Viewpoint - The article discusses the advancements in the biosynthesis of 1,4-butanediol (BDO) through engineered Escherichia coli, highlighting the challenges and breakthroughs in creating a sustainable production method without antibiotics or inducers [2][3][7]. Group 1: BDO Production Challenges - BDO biosynthesis faces three main challenges: lack of natural BDO-producing microorganisms, significant carbon loss during synthesis, and high dependency on antibiotics and inducers, leading to increased costs [3]. Group 2: Engineering Breakthroughs - Researchers at Zhejiang University have developed a high-efficiency BDO synthesis strain by systematically engineering E. coli, resulting in a production of 0.1 g/L of BDO initially, which was later optimized to 0.82 g/L [6]. - The optimal enzyme combination for BDO production was identified, including enzymes from various bacteria, and a mutant enzyme variant was created that increased BDO yield by 11.19 times [6]. - By knocking out the pdhR gene, the researchers enhanced the conversion efficiency of pyruvate to acetyl-CoA, significantly reducing pyruvate accumulation and increasing BDO yield by 44% to 1.83 g/L [6]. Group 3: Antibiotic-Free Fermentation System - A significant advancement was the development of an antibiotic-free fermentation system, where the researchers utilized E. coli's native transcriptional regulatory elements to drive BDO synthesis without external inducers [7]. - The engineered strain B21-pT19 achieved a remarkable BDO production of 34.63 g/L in a 5 L reactor over 72 hours, maintaining stable yields across multiple fermentation batches without the need for antibiotics or inducers, marking the highest reported level of BDO production to date [7].