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<p>Menaquinone-7, a form of vitamin K<sub>2</sub>, 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 <i>Bacillus subtilis</i> BS<i>-</i>Δ<i>ackA</i>. Through regression analysis and consideration of practical production constraints, the optimal fermentation medium parameters were determined as follows: 20&#xa0;g/L sucrose, 20.7&#xa0;g/L glycerol, 47.3&#xa0;g/L soy peptone, 4&#xa0;g/L yeast extract, and 1.9&#xa0;g/L KH<sub>2</sub>PO<sub>4</sub>, 0.1&#xa0;g/L MgSO<sub>4</sub>·7&#xa0;H<sub>2</sub>O. Under these optimized conditions, the MK-7 yield reached 154.6 ± 1.32&#xa0;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.</p>

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Enhancement of Menaquinone-7 production in Bacillus subtilis by optimizing the medium components through response surface methodology

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月29日

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  • Rui Zhang,
  • Han Wang,
  • Li Wang,
  • Zhiming Zheng

摘要

Menaquinone-7, a form of vitamin K2, 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 Bacillus subtilis BS-ΔackA. 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 KH2PO4, 0.1 g/L MgSO4·7 H2O. 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.