EFFICIENT PRODUCTION OF SECRETED PROTEINS BY ASPERGILLUS - PROGRESS, LIMITATIONS AND PROSPECTS

Filamentous fungi are widely used for the production of homologous and heterologous proteins but, compared to homologous proteins, the level s of production of heterologous proteins are usually low. During the l ast 5 years, the levels of production of heterologous proteins have be en drastically improved by fusing the corresponding gene to the 3' end of a homologous gene, encoding a well-secreted protein such as glucoa mylase. Nevertheless, little research has been carried out to determin e the limitations that hamper heterologous protein production. Recentl y we have carried out a detailed analysis of the levels of production of several proteins and glucoamylase fusion proteins in defined recomb inant Aspergillus awamori strains. In this review we will focus on the use of filamentous fungi for the production of heterologous, especial ly non-fungal, proteins. In particular, the effect of gene-fusion stra tegies will be reviewed. Furthermore, the remaining limitations in het erologous protein production and suggestions for improvement strategie s for overproduction of these protein will be discussed.