Application of genetic engineering for strain improvement in filamentous fungi

Inherent characteristics of filamentous fungi such as the ability to grow on cheap cultivation media and excellent protein secretion makes them competitive production organisms when compared to the eukaryotic yeast, animal, plant, and insect cell systems. One of the principal aims in fungal strain improvement discussed in this Chapter is yield enhancement of a particular protein that is secreted into the cultivation medium. Early strain development programs were based on the application of random mutagenesis and screening of the mutagenized cells for specific characteristics (Rowlands 1984). This method has been particularly successful in the isolation of high protein-secreting mutant strains that are currently being used as expression hosts for both homologous and heterologous gene products (DunnColeman et al. 1991; Nevalainen et al. 1994a; Mäntylä et al. 1998). Currently, molecular techniques such as increasing the gene copy numbers as well as performing gene knockouts are being applied for the further refinement of fungal products and production systems [e.g., Mäntylä et al. (1998)]. A number of research programs discussed in this Chapter and elsewhere in this volume, have been initiated in order to better understand the complex genetic networks involved in gene expression and protein secretion in filamentous fungi