系统代谢工程
Search documents
江南大学刘立明团队 | 最牛菌株!1,3-PDO发酵产量达到122.7 g/L
合成生物学与绿色生物制造· 2025-09-17 09:50
Core Viewpoint - The article discusses the advancements in the production of 1,3-propanediol (1,3-PDO) using engineered strains of Klebsiella pneumoniae, highlighting significant improvements in yield and efficiency through metabolic engineering and strain evolution [2][20][23]. Summary by Sections 1. Production Methodology - 1,3-PDO is a high-value fine chemical used in cosmetics, pharmaceuticals, and plastics, traditionally produced through chemical synthesis, which involves toxic substances and high pressure. Microbial fermentation has emerged as a more economical and environmentally friendly production method [2]. - The research team led by Professor Liu Liming achieved a production yield of 138.6 g/L of 1,3-PDO using the engineered strain FMME-51, with a conversion rate of 0.52 g/g, without the need for additional VB12 [2][20]. 2. Strain Optimization - Initial strain FMME-01 produced 67.2 g/L of 1,3-PDO but generated multiple by-products that reduced yield. Subsequent modifications led to strain FMME-14, which showed improved production performance [6]. - Further optimization of the cell membrane composition in strain FMME-38 resulted in a 62.5% increase in tolerance to high 1,3-PDO concentrations and a 41.2% reduction in cell death [9][10]. 3. Enhancements in Co-Factor Synthesis - The production process relies on VB12 and NADH. The integration of genes responsible for VB12 synthesis into the genome of strain FMME-48 resulted in a VB12 concentration of 50.8 μg/L and a 1,3-PDO yield of 118.3 g/L [14]. - The dynamic regulation of NADH levels was achieved through the construction of a biosensor-based system, enhancing the NADH/NAD⁺ ratio by 31.3% in strain FMME-51, leading to a 12.3% increase in 1,3-PDO yield [18][14]. 4. Process Optimization - The optimization of glycerol feeding rates and pH levels significantly improved the production performance of strain FMME-51, achieving a 1,3-PDO yield of 135.9 g/L at a pH of 6.8 [19]. - The final optimized strain FMME-51 demonstrated a production capacity of 122.7 g/L of 1,3-PDO using low-cost crude glycerol as a substrate, showcasing its industrial potential [20][23]. 5. Industrial Implications - The research indicates a significant advancement in the bioproduction of 1,3-PDO, achieving unprecedented yields and efficiencies while eliminating the need for expensive co-factors, thus reducing production costs [20][23]. - The ability of engineered strain FMME-51 to efficiently utilize crude glycerol highlights its potential for large-scale industrial applications in the production of high-value chemicals [23].
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
合成生物学与绿色生物制造· 2025-07-06 04:05
【SynBioCon】 获 悉 ,近期, 浙江工业大学郑裕国院士团队柳志强教授课题组 采用模块化途径工程、酶筛选、sRNA 引导的瓶颈识别、微调关键代谢节点、辅因子工程和发酵优化等系统代谢工程策略,开发了一种无质粒、无营养缺陷的 OAH高产菌株OAH37,将OAH发酵产量增产至 94.1 g/L ,创目前报道最高纪录,为OAH的绿色生物制造奠定了坚实基 础。 图1 OAH的代谢途径及其增产策略示意图 主要研究内容及其关键技术突破: 1. 「L-高丝氨酸+MetX」双模块加强,促进OAH初步积累 团队以前期构建的L-高丝氨酸生产菌株HSY6为底盘,通过质粒引入MetX确定该底盘具备OAH合成能力,产量为5.29 g/L。随后,回补了L-赖氨酸和甲硫氨酸途径,以减少菌株的营养缺陷;进一步整合天冬氨酸转氨酶( aspB cg )、谷氨 酸合酶( gltAB bs )和天冬氨酸激酶( lysC pa ),以增强L-高丝氨酸模块的代谢通量。通过异源MetX的筛选,发现来 源于海洋环状菌( Cyclobacterium marinum )的 metX cm 整合至假基因位点可将产量提升至8.30 g/L,相较于初始菌 株 ...