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利用原位细胞截留生物反应器提高桃儿七鬼臼毒素产量。

Enhanced production of podophyllotoxin by Podophyllum hexandrum using in situ cell retention bioreactor.

作者信息

Chattopadhyay Saurabh, Bisaria Virendra S, Srivastava Ashok K

机构信息

Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, India.

出版信息

Biotechnol Prog. 2003 May-Jun;19(3):1026-8. doi: 10.1021/bp025765k.

DOI:10.1021/bp025765k
PMID:12790673
Abstract

The rhizomes of the rare plant Podophyllum hexandrum contain podophyllotoxin, which is a precursor of the anticancer drugs etoposide and teniposide. Batch cultivation of Podophyllum hexandrum was conducted using optimized medium in a 3 L bioreactor, which resulted in biomass and podophyllotoxin concentrations of 21.4 g/L and 13.8 mg/L in 24 and 26 days, respectively. The batch kinetics was used to identify the mathematical model. The model was extrapolated to identify the nutrient feeding rate (150 mL/d) and substrate concentration (105 g/L) in the incoming feed for nonlimiting and noninhibitory glucose concentration in the cell retention bioreactor. An improvement in cell growth to 53 g/L and intracellular podophyllotoxin accumulation of 48.8 mg/L was achieved in 60 days, when the bioreactor was operated in continuous cell retention cultivation mode.

摘要

珍稀植物喜马拉雅鬼臼的根茎含有鬼臼毒素,它是抗癌药物依托泊苷和替尼泊苷的前体。在3升生物反应器中使用优化培养基对喜马拉雅鬼臼进行分批培养,分别在24天和26天得到了生物量浓度为21.4克/升和鬼臼毒素浓度为13.8毫克/升的结果。采用分批动力学来确定数学模型。该模型经外推以确定细胞保留生物反应器中进料的营养物进料速率(150毫升/天)和底物浓度(105克/升),使葡萄糖浓度既无限制又无抑制作用。当生物反应器以连续细胞保留培养模式运行时,在60天内细胞生长提高到53克/升,细胞内鬼臼毒素积累量达到48.8毫克/升。

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