Plant Research Department, Nuclear Research Center, Atomic Energy Authority, Cairo, Egypt.
Department of Botany and Microbiology, Faculty of Science, Zagazig University, Zagazig, Egypt.
Bioprocess Biosyst Eng. 2020 Jun;43(6):997-1008. doi: 10.1007/s00449-020-02295-8. Epub 2020 Jan 30.
Taxol is the most profitable drug ever developed in cancer chemotherapy; however, the market demand for the drug greatly exceeds the supply that can be sustained from its natural sources. In this study, Aspergillus fumigatus TXD105-GM6 and Alternaria tenuissima TER995-GM3 were immobilized in calcium alginate beads and used for the production of taxol in shake flask cultures. In an effort to increase the taxol magnitude, immobilization conditions were optimized by response surface methodology program (RSM). The optimum levels of alginate concentration, calcium chloride concentration, and mycelium fresh weight were 5%, 4%, and 15% (w/v), respectively. Under these conditions, taxol production by the respective fungal strains was intensified to 901.94 μg L and 529.01 μg L. Moreover, the immobilized mycelia of both strains were successfully used in the repeated production of taxol for six different fermentation cycles. The total taxol concentration obtained in all cycles reached 4540.14 μg L by TXD105-GM6 and 2450.27 μg L by TER995-GM3 strain, which represents 7.85- and 6.31-fold increase, as compared to their initial titers. This is the first report on the production of taxol in semi-continuous fermentation. To our knowledge, the taxol productivity achieved in this study is the highest reported by academic laboratories for microbial cultures which indicates the future possibility to reduce the cost of taxol production.
紫杉醇是癌症化疗中开发的最有利可图的药物；然而，药物的市场需求远远超过了从天然来源可持续供应的水平。在这项研究中，木霉 TXD105-GM6 和细极链格孢 TER995-GM3 被固定在海藻酸钠珠中，并用于摇瓶培养生产紫杉醇。为了提高紫杉醇的产量，通过响应面法程序（RSM）优化了固定化条件。海藻酸钠浓度、氯化钙浓度和菌丝鲜重的最佳水平分别为 5%、4%和 15%（w/v）。在这些条件下，分别提高了真菌菌株的紫杉醇产量 901.94μg/L 和 529.01μg/L。此外，两种菌株的固定化菌丝体在六个不同发酵周期的紫杉醇重复生产中得到了成功应用。通过 TXD105-GM6 获得的总紫杉醇浓度在所有周期中达到 4540.14μg/L，通过 TER995-GM3 菌株达到 2450.27μg/L，分别比初始滴度提高了 7.85 倍和 6.31 倍。这是半连续发酵生产紫杉醇的首次报道。据我们所知，本研究中实现的紫杉醇生产率是学术实验室报道的微生物培养物中最高的，这表明未来有可能降低紫杉醇生产的成本。
