Environmental Diseases Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.
Department of Systems Biotechnology, Chung-Ang University, Anseong 17546, Republic of Korea.
J Microbiol Biotechnol. 2021 Dec 28;31(12):1624-1631. doi: 10.4014/jmb.2109.09039.
Prodigiosin as a high-valued compound, which is a microbial secondary metabolite, has the potential for antioxidant and anticancer effects. However, the large-scale production of functionally active -derived prodigiosin by fermentation in a cost-effective manner has yet to be achieved. In the present study, we established carbon source-optimized medium conditions, as well as a procedure for producing prodigiosin by fermentation by culturing using 10 L and 200 L bioreactors. Our results showed that prodigiosin productivity using 250 ml flasks was higher in the presence of glucose than other carbon sources, including mannose, sucrose, galactose, and fructose, and could be scaled up to 10 L and 200 L batches. Productivity in the glucose (2.5 g/l) culture while maintaining the medium at pH 6.89 during 10 days of cultivation in the 200 L bioreactor was measured and increased more than productivity in the basal culture medium in the absence of glucose. Prodigiosin production from 10 L and 200 L fermentation cultures of was confirmed by high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) analyses for more accurate identification. Finally, the anticancer activity of crude extracted prodigiosin against human cancerous leukemia THP-1 cells was evaluated and confirmed at various concentrations. Conclusively, we demonstrate that culture conditions for using a bioreactor with various parameters and ethanol-based extraction procedures were optimized to mass-produce the marine bacterium-derived high purity prodigiosin associated with anti-cancer activity.
灵菌红素作为一种高价值的化合物,是一种微生物次生代谢产物,具有抗氧化和抗癌作用。然而,通过发酵以经济有效的方式大规模生产具有功能活性的衍生灵菌红素尚未实现。在本研究中,我们建立了碳源优化的培养基条件,以及通过在 10 L 和 200 L 生物反应器中培养来发酵生产灵菌红素的程序。我们的结果表明,在存在葡萄糖的情况下,使用 250 ml 摇瓶培养时灵菌红素的生产力高于其他碳源,包括甘露糖、蔗糖、半乳糖和果糖,并且可以扩大到 10 L 和 200 L 批次。在 200 L 生物反应器中培养 10 天期间,在维持培养基 pH 值为 6.89 的情况下,葡萄糖(2.5 g/l)培养物中的生产力高于基础培养基中没有葡萄糖时的生产力。通过高效液相色谱(HPLC)和液相色谱-质谱(LC-MS)分析从 10 L 和 200 L 的发酵培养物中确认了 的灵菌红素生产,以进行更准确的鉴定。最后,评估并证实了粗提灵菌红素对人白血病 THP-1 细胞的抗癌活性在不同浓度下的活性。总之,我们证明了使用具有各种参数的生物反应器和基于乙醇的提取程序的 培养条件已被优化,可以大规模生产与抗癌活性相关的海洋细菌衍生的高纯度灵菌红素。