Regulation of secreted protein production by filamentous fungi: recent developments and perspectives.

Filamentous fungi, typically, are saprophytic organisms which, unlike yeasts, secrete a wide array of enzymes involved in the breakdown and recycling of complex polymers from both plant and animal tissues. This makes them attractive hosts for the production of secreted heterologous proteins (Jeenes et al., 1991; van den Hondel et al., 1991). In only a few examples, however, have the secreted yields of heterologous protein reached the gram per litre levels of many homologous fungal enzymes. In many cases, the problem does not appear to be at the level of transcription but, rather, occurs within the secretory pathway. Although the secretory process has barely been explored in filamentous fungi, we have attempted to identify areas upon which attention should be focused based on current knowledge gained from other systems. We also discuss recent developments in the dissection of transcriptional control in these organisms with particular reference to the interaction of regulatory proteins with fungal promoter regions and to the need for targeting expression cassettes to specific locations in the fungal genome. Understanding the detailed mechanisms of transcriptional control will help in designing modified promoter elements or regulatory factors optimized for a given set of growth conditions. Coupled with the proposed study of the secretory pathway, this should improve the yields of secreted heterologous proteins produced by filamentous fungi.