Xu Shuo, Li Qian, Li Ye, Zhang Yue, Li Qing, Ji Liyun, Cheng Hairong
State Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
Appl Environ Microbiol. 2025 Apr 23;91(4):e0006125. doi: 10.1128/aem.00061-25. Epub 2025 Mar 26.
Erythritol, a food additive, is produced on an industrial scale using the yeast . Nevertheless, the key performance indicators (KPIs) have been found to be unsatisfactory, resulting in elevated erythritol production cost. This study demonstrated that the KPIs (titer, productivity, and yield) of erythritol can be improved by the synergistic application of transporter and pathway engineering strategies in the producing strain. The engineered strain Ylxs48 exhibits a glucose consumption rate of 310 g/L of glucose within 46 h during batch culture in 3, 100, and 200 L bioreactors as compared to above 72 h for the parental strain Ylxs01. The erythritol yield achieved ranges from 0.69 to 0.74 g/g depending on the culture conditions as compared to 0.55-0.57 g/g for the parental strain Ylxs01. The productivity surpasses 4.60 g/(L·h), representing a 1.91-fold improvement over the parental strain Ylxs01 in 3, 100, or 200 L bioreactors. Under fed-batch conditions in a 200 L bioreactor, an erythritol titer of 355.81 g/L was achieved, marking the highest titer ever reported. This increased erythritol titer enabled crystallization at 4°C directly from the clear supernatant, eliminating the requirement for evaporation or concentration steps. A comprehensive techno-economic analysis of the entire process conclusively demonstrated that implementing the industrial process based on the engineered strain Ylxs48 led to a significant 23% reduction in production cost. This approach holds the potential to substantially reduce erythritol costs and provides novel insights for engineering other industrial strains.
The expansion of the erythritol market attracted excessive capital injection, resulting in overcapacity, operational difficulties, and even bankruptcy of erythritol manufacturers. Technology upgrades in the industry are imminent. However, the production technology of existing enterprises is seriously homogenized, and there is a lack of competitive core-producing strains. In this study, the industrial erythritol-producing strain CGMCC7326 was genetically modified by integrating substrate transport and pathway modification, which improved the conversion of glucose and significantly improved KPIs, thereby reducing the erythritol production cost.
赤藓糖醇是一种食品添加剂,通过酵母进行工业规模生产。然而,关键性能指标(KPI)并不理想,导致赤藓糖醇生产成本升高。本研究表明,通过在生产菌株中协同应用转运体和途径工程策略,可以提高赤藓糖醇的关键性能指标(滴度、生产率和产量)。在3升、100升和200升生物反应器中进行分批培养时,工程菌株Ylxs48在46小时内的葡萄糖消耗率为310克/升葡萄糖,而亲本菌株Ylxs01则需要72小时以上。根据培养条件,赤藓糖醇产量在0.69至0.74克/克之间,而亲本菌株Ylxs01为0.55 - 0.57克/克。生产率超过4.60克/(升·小时),在3升、100升或200升生物反应器中比亲本菌株Ylxs01提高了1.91倍。在200升生物反应器的补料分批培养条件下,赤藓糖醇滴度达到355.81克/升,这是有报道以来的最高滴度。这种提高的赤藓糖醇滴度使得能够在4°C下直接从澄清的上清液中结晶,无需蒸发或浓缩步骤。对整个过程进行的全面技术经济分析最终表明,基于工程菌株Ylxs48实施工业生产工艺可使生产成本显著降低23%。这种方法有可能大幅降低赤藓糖醇成本,并为改造其他工业菌株提供新的见解。
赤藓糖醇市场的扩张吸引了过多资本注入,导致产能过剩、运营困难,甚至赤藓糖醇制造商破产。行业技术升级迫在眉睫。然而,现有企业的生产技术严重同质化,缺乏具有竞争力的核心生产菌株。在本研究中,通过整合底物转运和途径改造对工业赤藓糖醇生产菌株CGMCC7326进行了基因改造,提高了葡萄糖转化率并显著改善了关键性能指标,从而降低了赤藓糖醇生产成本。