Comparative gene expression profiling reveals key changes in expression levels of cephalosporin C biosynthesis and transport genes between low and high-producing strains of Acremonium chrysogenum.

Transcript levels of several key genes responsible for cephalosporin C (CPC) biosynthesis and transport have been determined using qPCR analysis of Acremonium chrysogenum strains differing more than 100-fold in the levels of CPC production. The expression of genes involved in the final steps of CPC production was significantly increased in the high-producing RNCM F-4081D strain compared to the wild-type ATCC 11550 strain. Different dynamics in the course of cultivation was observed for the genes known to be involved in the transport of CPC intermediates between subcellular compartments. Overall, comparative expression analysis showed balanced and fine-tuned expression of the genes responsible for CPC biosynthesis and transport in the genetically selected A. chrysogenum RNCM F-4081D strain, reflecting its capacity to overcome known CPC biosynthesis "bottlenecks" and produce CPC of high yield and purity.