Optimal gene expression and amplification strategies for batch and continuous recombinant cultures

The use of regulated promoters and plasmid replication controls amenable to environmental manipulation offers the opportunity of reconciling the opposing effects of cloned-gene content and expression level on process productivity. Regulated replicons and promoters offer the biochemical engineer the opportunity to optimize process performance through application of optimized environmental changes that in turn generate optimal profiles of plasmid content and cloned-gene expression levels during the course of the process. In order to explore the influence of different operating strategies on recombinant culture product accumulation and also to examine the effects of different assumptions concerning host-plasmid interactions, a mathematical model previously formulated to describe product formation in unstable recombinant cultures has been used. Responses of this model to different induction and amplification strategies have been calculated for batch and continuous bioreactors.