Nutritional and engineering aspects of microbial process development.

Prakash S Masurekar
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引用次数: 37

Abstract

Today we use many drugs produced by microorganisms. However, when these drugs were discovered it was found that the yields were low and a substantial effort had to be put in to develop commercially viable processes. A key part of this endeavor was the studies of the nutritional and the engineering parameters. In this chapter, the basic principles of optimizing the nutritional and engineering aspect of the production process are described with appropriate examples. It was found that two critical components of nutritional medium, carbon and nitrogen source regulated the synthesis of the compounds of interest. Rapidly utilizable carbon source such as glucose supported the growth but led to catabolite repression and alternative carbon sources or methods of addition had to be devised. Inorganic nitrogen sources led to undesirable changes in pH of the medium. Organic nitrogen sources could influence the yields positively or negatively and had to be chosen carefully. Essential nutrients like phosphates often inhibited the synthesis and its concentration had to be maintained below the inhibitory levels. On many occasions, trace nutrients like metal ions and vitamins were found to be critical for good production. Temperature and pH were important environmental variables and their optimum values had to be determined. The media were designed and optimized initially with 'one variable at a time' approach and later with experimental design based on statistics. The latter approach is preferred because it is economical, considers interactions between medium components and allows rapid optimization of the process. The engineering aspects like aeration, agitation, medium sterilization, heat transfer, process monitoring and control, become critical as the process is scaled-up to the production size. Aeration and agitation are probably the most important variables. In many processes dissolved oxygen concentration had to be maintained above a critical value to obtain the best yields. The rheological properties of fermentation broth significantly affect the aeration and mixing efficiency. The removal of heat from the large fermentors can be difficult under certain conditions. However, new designs of impellers, availability of sensors to monitor important physiological and process variables and advent of computers have facilitated successful scale-up of fermentation processes.

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微生物过程开发的营养和工程方面。
今天我们使用许多由微生物产生的药物。然而,当这些药物被发现时,人们发现产量很低,必须投入大量的努力来开发商业上可行的工艺。这一努力的关键部分是营养和工程参数的研究。在本章中,通过适当的例子描述了优化生产过程的营养和工程方面的基本原则。研究发现,营养培养基中碳源和氮源两种关键成分调控了目标化合物的合成。快速利用的碳源如葡萄糖支持生长,但导致分解代谢抑制,必须设计替代碳源或添加方法。无机氮源导致了培养基pH值的不良变化。有机氮源对产量有积极或消极的影响,必须慎重选择。必需的营养物质如磷酸盐经常抑制合成,其浓度必须保持在抑制水平以下。在很多情况下,微量营养物质,如金属离子和维生素,被发现是良好生产的关键。温度和pH值是重要的环境变量,必须确定它们的最佳值。培养基的设计和优化最初采用“一次一个变量”的方法,后来采用基于统计学的实验设计。后一种方法是首选的,因为它经济,考虑到中间组件之间的相互作用,并允许过程的快速优化。工程方面,如曝气、搅拌、介质灭菌、传热、过程监测和控制,随着工艺扩大到生产规模,变得至关重要。通气和搅拌可能是最重要的变量。在许多工艺中,溶解氧浓度必须保持在临界值以上才能获得最佳收率。发酵液的流变特性对曝气和混合效率有显著影响。在某些条件下,从大型发酵罐中去除热量可能是困难的。然而,新的叶轮设计、监测重要生理和过程变量的传感器的可用性以及计算机的出现促进了发酵过程的成功扩大。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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