Zhang Rui, Wang Han, Wang Li, Zheng Zhiming
College of Life Sciences, Anhui Medical University, Hefei, 230012, Anhui, China.
Institute of Intelligent Machines, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, China.
Bioresour Bioprocess. 2025 Aug 29;12(1):93. doi: 10.1186/s40643-025-00934-0.
Menaquinone-7, a form of vitamin K, plays a critical role in the treatment of hemorrhagic diseases caused by vitamin K deficiency and in the prevention of bone fractures. Microbial fermentation has emerged as a promising method for MK-7 production due to its high product optical purity and significant physiological activity. However, the current production efficiency of MK-7 remains insufficient to meet industrial demands. In this study, we employed a combination of single-factor experiments, Plackett-Burman design, steepest ascent experiments, and Box-Behnken design to optimize the fermentation medium for MK-7 production by BSΔ. Through regression analysis and consideration of practical production constraints, the optimal fermentation medium parameters were determined as follows: 20 g/L sucrose, 20.7 g/L glycerol, 47.3 g/L soy peptone, 4 g/L yeast extract, and 1.9 g/L KHPO, 0.1 g/L MgSO·7 HO. Under these optimized conditions, the MK-7 yield reached 154.6 ± 1.32 mg/L. The experimental results demonstrated excellent stability and reliability, aligning closely with the model predictions. This study significantly enhances MK-7 production at the shake-flask fermentation level, providing valuable insights for large-scale industrial applications.
甲萘醌-7（维生素K的一种形式）在治疗维生素K缺乏引起的出血性疾病以及预防骨折方面发挥着关键作用。由于微生物发酵生产的甲萘醌-7具有高产品光学纯度和显著的生理活性，它已成为一种有前景的生产方法。然而，目前甲萘醌-7的生产效率仍不足以满足工业需求。在本研究中，我们采用单因素实验、Plackett-Burman设计、最速上升实验和Box-Behnken设计相结合的方法，对BSΔ生产甲萘醌-7的发酵培养基进行优化。通过回归分析并考虑实际生产限制，确定了最佳发酵培养基参数如下：蔗糖20 g/L、甘油20.7 g/L、大豆蛋白胨47.3 g/L、酵母提取物4 g/L、KHPO 1.9 g/L、MgSO·7HO 0.1 g/L。在这些优化条件下，甲萘醌-7产量达到154.6±1.32 mg/L。实验结果显示出优异的稳定性和可靠性，与模型预测结果紧密吻合。本研究显著提高了摇瓶发酵水平下甲萘醌-7的产量，为大规模工业应用提供了有价值的见解。
