Production of the anticancer drug taxol by the endophytic fungusEpicoccum nigrumTXB502: enhanced production by gamma irradiation mutagenesis and immobilization technique
Production of the anticancer drug taxol by the endophytic fungusEpicoccum nigrumTXB502: enhanced production by gamma irradiation mutagenesis and immobilization technique
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DOI：
10.1007/s00253-020-10712-x
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发表时间：
2020-07-02
影响因子：
5
通讯作者：
Ismaiel, Ahmed A.
中科院分区：
文献类型：
--
作者：
El-Sayed, El-Sayed R.;Zaki, Amira G.;Ismaiel, Ahmed A.
紫杉醇是一种植物提取的二萜类化合物，是癌症化疗中商业上最需要的药物。尽管紫杉醇的微生物生产是成功且具有前景的，但所报道的产量仍然不足以进行大规模生产。因此，发现新的紫杉醇生产微生物菌株以及工艺优化、菌株改良和固定化技术等增产方法是主要目标。本文从红豆杉中分离得到一株产紫杉醇的起始菌株Epicocum nigrumTXB502（初始产量61.35 mu g L-1），并通过形态学和分子工具鉴定。通过一次测试一个参数来评估最佳栽培和营养条件，结果使产量显着增加了 88.59%。 In addition, a stable mutant with improved productivity (40.07% yield increase in comparison with the parent strain) was successfully developed after gamma irradiation mutagenesis of the start strain.通过测试该突变体孢子和菌丝体的不同固定化载体，进一步提高了紫杉醇效价。使用藻酸盐固定的菌丝体实现了紫杉醇的过量生产，并且可以以半连续的形式进行六个连续的生产周期。最终总浓度达到8187.77μg紫杉醇6L(-1)，与起始菌株的初始滴度相比，增加了约22倍。这些发现可以为紫杉醇的未来工业制造铺平道路，因为本研究中实现的紫杉醇产量是微生物培养学术实验室报告的最高水平。
Taxol, a phyto-extracted diterpenoid, is the most commercially needed drug in cancer chemotherapy. In spite of the microbial production of taxol being successful and prospective, the reported yields are still not sufficient for large-scale production. Thus, the discovery of new taxol-producing microbial strains and production enhancement methodologies such as process optimization, strain improvement, and immobilization technique are the main objectives. In this paper, a taxol-producing start strainEpicoccum nigrumTXB502 (initial yield 61.35 mu g L-1) was isolated fromTaxus baccataand identified by morphological and molecular tools. The optimum cultivation and nutritional conditions were assessed by testing one parameter at a time approach that resulted in 88.59% significant production increase. In addition, a stable mutant with improved productivity (40.07% yield increase in comparison with the parent strain) was successfully developed after gamma irradiation mutagenesis of the start strain. The taxol titer was further improved via testing different immobilization carriers for both spores and mycelia of this mutant. Over taxol production was achieved using alginate-immobilized mycelia with the feasibility of conducting six successive production cycles in a semi-continuous form. The final total concentration reached 8187.77 mu g taxol 6 L(-1)which represents approximately 22-fold increase, as compared to the initial titer of the start strain. These findings can pave the way for the prospective industrial manufacturing of taxol, as the achieved taxol production in this study is the highest reported by academic laboratories for microbial cultures.