TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL EVENTS AFFECT THE PRODUCTION OF SECRETED HEN EGG-WHITE LYSOZYME BY ASPERGILLUS-NIGER

The relationship between heterologous gene copy number, mRNA and secreted protein yields has been studied in Aspergillus niger transformants containing either the hen egg-white lysozyme (HEWL) cDNA gene or a glucoamylase-HEWL gene fusion (incorporating the A. niger glaA gene). The results support a direct relationship between HEWL gene copy number, mRNA and secreted HEWL protein levels at low (<25) copy numbers. High protein yields are associated with multiple copies of the recombinant gene at a single site. Fusion of the HEWL gene to the glucoamylase gene resulted in higher steady-state levels of heterologous mRNA. Transformants with the HEWL cDNA alone exhibited a ten-fold higher mRNA:protein ratio than transformants with the gene fusion indicating that post-transcriptional events significantly affect final secreted protein yields.