Ertola R J, Giulietti A M, Castillo F J
University of La Plata, Argentina.
Bioprocess Technol. 1995;21:89-137.
The fundamental knowledge available about the microorganism, substrates, and process represent the basis on which a rational approach for the design and formulation of media for microbial processes can be attempted. In this respect, it is necessary to analyze critically the main objective to be optimized (yield, productivity, quality of final product, etc.). The first step of medium development is concerned with the decision to be taken about the adequate components to be used, followed by the calculation of their concentrations. After medium preparation and experimentation, the application of the most appropriate statistical optimization methodology will make it possible to attain the optimal medium. Medium design and formulation for plant cell processes are still carried out on an empirical basis owing to the lack of fundamental knowledge. However, some general guidelines can be given for growth and production media considering the experimental evidence available about the functions and influence of the medium components for promoting growth and product formation. Adequate manipulation of the carbon, nitrogen, and phosphorus sources and phytohormones and the inclusion of precursors and elicitors in the medium represent the best strategy for improving medium development for plant cell processes. The development of cost-effective medium supplies for mammalian cell culture production of proteins is a key element for a commercially successful process. Medium development is a task that requires experience, time, and resources in its solutions, which may be several. An optimal formulation is elusive because there will always be room for improvement, but through systematic, comprehensive work, practical combinations of nutrients, factors, and feeding schedules can be developed in a reasonable time. A properly developed formulation can bring the burden of the medium below 10% of the total cost of a mammalian cell process.
关于微生物、底物和工艺的现有基础知识，是尝试采用合理方法设计和配制用于微生物工艺的培养基的基础。在这方面，有必要严格分析要优化的主要目标（产量、生产率、最终产品质量等）。培养基开发的第一步涉及决定使用何种合适的成分，随后计算其浓度。在制备培养基并进行实验后，应用最合适的统计优化方法将有可能获得最佳培养基。由于缺乏基础知识，植物细胞工艺的培养基设计和配制仍基于经验进行。然而，考虑到关于培养基成分促进生长和产物形成的功能及影响的现有实验证据，可为生长培养基和生产培养基提供一些通用指导原则。对碳源、氮源、磷源和植物激素进行适当调控，并在培养基中添加前体和诱导子，是改进植物细胞工艺培养基开发的最佳策略。开发具有成本效益的培养基供应体系以用于哺乳动物细胞培养生产蛋白质，是实现商业成功工艺的关键要素。培养基开发是一项在解决方案中需要经验、时间和资源的任务，可能有多种解决方案。最佳配方难以捉摸，因为总有改进的空间，但通过系统、全面的工作，可以在合理时间内开发出营养成分、因子和补料方案的实际组合。一个经过妥善开发的配方可以使培养基成本在哺乳动物细胞工艺总成本中所占比例低于10%。
