郑裕国院士团队柳志强教授组：实现大肠杆菌高产O-乙酰-L-高丝氨酸

Core Viewpoint - O-acetyl-L-homoserine (OAH) is a significant platform compound for producing L-methionine and other valuable chemicals, with recent advancements in sustainable production methods using E. coli, achieving a record yield of 94.1 g/L through innovative metabolic engineering strategies [1][16]. Group 1: Research Content and Key Technical Breakthroughs - The team enhanced OAH production by integrating a dual-module approach with L-homoserine and MetX, increasing initial yield from 5.29 g/L to 8.30 g/L, a 56.9% improvement [3]. - A dynamic regulation strategy for acetyl-CoA was developed, leading to an OAH yield of 11.59 g/L by optimizing multiple pathways and reducing competition [4]. - The use of sRNA for identifying rate-limiting steps in OAH synthesis revealed four critical areas for optimization, including precursor carbon flux distribution and amino supply [7]. - A multi-node fine-tuning approach led to a series of yield improvements, with the final strain OAH33 achieving 19.40 g/L by addressing nutrient deficiencies and optimizing metabolic pathways [12]. Group 2: Production Optimization Techniques - The innovative two-stage pH control in a 5 L bioreactor allowed for the efficient synthesis of OAH, achieving a yield of 94.1 g/L within 68.7 hours, enhancing production by 15.5%-37.3% compared to single pH control [16]. - The research demonstrated that the combination of ATP turnover enhancement and metabolic pathway optimization significantly improved OAH production, with the final strain OAH37 achieving a yield of 20.08 g/L, a 137% increase from the initial strain [14]. Group 3: Future Research and Development - The findings from this research are set to be published in "Metabolic Engineering" in July 2025, indicating ongoing advancements in the field of synthetic biology and metabolic engineering [17].