10 - Methods for laboratory process development

Summary

Introduction

The general problem

It is interesting to consider the problems that have to be solved in moving productivity towards high yields, based on a consideration of the material so far presented. While an increase in the specific productivity of the cells is important, many changes are also needed in primary metabolism and growth. Some of these are summarised in Tables 10.1 and 10.2. Table 10.1 lists some of the shifts in behaviour that are needed, while Table 10.2 shows some of the factors that have to be taken into account in both primary and secondary metabolism so as to obtain high yields.

Table 10.1 brings out the great differences between high-yielding and wild strains, especially the independence of secondary metabolism in relation to growth patterns and primary metabolism; the whole process of secondary metabolism becomes smoother and more flexible. Table 10.2 brings out the complexity of primary metabolism and the number of factors connected with it that have to be optimised to give good production. Secondary metabolism is, in comparison, simpler, though it depends on the properties of the cells being favourable to it. For the best results, secondary metabolism must be able to work well while primary metabolism is changing. Productivity is often connected to growth rate (μ). Productivity seems really to be related to the state of the cells. This may imply a particular value of μ, but cases arise where productivity is high, even in the absence of growth.

As mutation and selection take place, both good and bad effects are produced. It is possible that at some times primary metabolism may be optimal for production, and at other times it may be less good.