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在使用载体支持菌丝体生长的流化床生物反应器中生产青霉素。

Production of penicillin in a fluidized-bed bioreactor using a carrier-supported mycelial growth.

作者信息

Kim J H, Oh D K, Park S K, Park Y H, Wallis D A

机构信息

Biotechnology Division, The Korea Advanced Institute of Science and Technology, P.O. Box 137, Dong Dae Mun, Seoul, Korea.

出版信息

Biotechnol Bioeng. 1986 Dec;28(12):1838-44. doi: 10.1002/bit.260281211.

DOI:10.1002/bit.260281211
PMID:18555301
Abstract

A carrier-supported mycelial growth of Penicillium chrysogenum was applied to penicillin fermentation system using celite as a support material. Hyphal growth through the pore matrices of the material showed strong anchorages and provided highly stable biofilm growth. With bioparticles developed in such a manner, both cell growth and penicillin production were observed to increase significantly compared to the conventional dispersed filamentous cultures. Maximum values of specific penicillin production rate were found to be constant regardless of the growth form. A three-phase fluidized-bed fermentor was designed and tested for penicillin production using the bioparticles. Two modes of operation, semicontinuous and repeated fed batch, of the fermentor were tried. It was noted that the overgrowth of free mycelia and the development of fluffy loose bioparticles caused poor mixing and made the fermentor operation quite difficult. Control of the bioparticle size and the extension of production phase were therefore considered important to maintain the reactor productivity at a desired level. From the results of repeated fed-batch operation it was found that the control of bioparticle size could be successfully achieved by phosphate-limiting culture condition. Penicillin production under this condition was also observed to be maintained at a high level (about 80% of the maximum) for at least 1 month.

摘要

以硅藻土为载体材料,将产黄青霉在载体上支持的菌丝体生长应用于青霉素发酵系统。菌丝通过材料的孔隙基质生长,显示出很强的附着力,并提供了高度稳定的生物膜生长。用这种方式制备的生物颗粒,与传统的分散丝状培养相比,细胞生长和青霉素产量均显著增加。发现比青霉素生产率的最大值与生长形式无关,保持恒定。设计并测试了一种使用生物颗粒生产青霉素的三相流化床发酵罐。尝试了该发酵罐的两种操作模式,即半连续和重复补料分批操作。注意到游离菌丝体的过度生长和蓬松松散生物颗粒的形成导致混合不良,使发酵罐操作相当困难。因此,控制生物颗粒大小和延长生产阶段对于将反应器生产力维持在所需水平很重要。从重复补料分批操作的结果发现,通过磷酸盐限制培养条件可以成功实现生物颗粒大小的控制。在此条件下,青霉素产量也至少1个月保持在较高水平(约为最大值的80%)。

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Biotechnol Bioeng. 1986 Dec;28(12):1838-44. doi: 10.1002/bit.260281211.
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Penicillin fermentation in a 200-liter tower fermentor using cells confined to microbeads.在一个200升塔式发酵罐中使用固定在微珠中的细胞进行青霉素发酵。
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[Penicillium chrysogenum mycelial productivity in the 1st phase of penicillin biosynthesis].[产黄青霉在青霉素生物合成第一阶段的菌丝体生产力]
Antibiotiki. 1978 Jan;23(1):3-7.

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