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在生物膜反应器中,通过纳豆芽孢杆菌生产维生素 K(甲萘醌-7)的分批补料策略的实施。

Implementation of fed-batch strategies for vitamin K (menaquinone-7) production by Bacillus subtilis natto in biofilm reactors.

机构信息

Department of Agricultural and Biological Engineering, The Pennsylvania State University, University Park, PA, 16802, USA.

Faculty of Science and Engineering, The University of Waikato, Hamilton, 3240, New Zealand.

出版信息

Appl Microbiol Biotechnol. 2018 Nov;102(21):9147-9157. doi: 10.1007/s00253-018-9340-7. Epub 2018 Sep 14.

Abstract

Recent studies show the essential health benefits associated with vitamin K, especially menaquinone-7 (MK-7). These benefits include reducing risks of cardiovascular diseases, osteoporosis, and even cancer. However, MK-7 production on an industrial level is only possible through bacterial fermentation and also current static fermentation strategies are not potent enough with difficulties to scale up. Biofilm reactors, however, may be a practical alternative. Biofilm reactors provide a controlled environment for the microorganisms to form mature and robust biofilms that enable them to produce value-added products with enhanced efficiencies. In this study, fed-batch addition of glucose and glycerol were investigated to the base media in biofilm reactors, as carbon source addition seemed crucial in batch fermentations. Results indicated that fed-batch strategies can be significantly effective in glucose-based medium, increasing the end-product concentrations to 28.7 ± 0.3 mg/L of MK-7 which was 2.3 fold higher than the level produced in suspended-cell bioreactors and renders the biofilm reactors as a potential replacement for static fermentation strategies. Moreover, morphological changes of B. subtilis were tracked during the 12-day long fermentation runs and finally, SEM investigations confirmed significant biofilm and extracellular matrices formed on the plastic composite support (PCS) in the biofilm reactors. In conclusion, biofilm reactors especially with fed-batch fermentation regimes seem to be an effective tool for MK-7 production at industrial scales.

摘要

最近的研究表明,维生素 K,特别是甲萘醌-7(MK-7)对健康有重要的益处。这些益处包括降低心血管疾病、骨质疏松症甚至癌症的风险。然而,MK-7 在工业水平上的生产只能通过细菌发酵来实现,而且目前的静态发酵策略还不够强大,难以扩大规模。生物膜反应器可能是一种实用的替代方法。生物膜反应器为微生物提供了一个受控的环境,使它们能够形成成熟而强大的生物膜,从而以更高的效率生产增值产品。在这项研究中,研究了在生物膜反应器中向基础培养基中分批添加葡萄糖和甘油作为碳源,因为在分批发酵中,碳源的添加似乎是至关重要的。结果表明,分批添加策略在基于葡萄糖的培养基中非常有效,将终产物浓度提高到 28.7±0.3mg/L 的 MK-7,比悬浮细胞生物反应器中产生的水平高 2.3 倍,使生物膜反应器成为静态发酵策略的潜在替代品。此外,在 12 天的发酵过程中跟踪了枯草芽孢杆菌的形态变化,最后,SEM 研究证实了生物膜反应器中在塑料复合载体(PCS)上形成了大量的生物膜和细胞外基质。总之,生物膜反应器,特别是采用分批补料发酵策略,似乎是在工业规模上生产 MK-7 的有效工具。

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