Making recombinant proteins in filamentous fungi- are we expecting too much?

摘要: Hosts used for the production of recombinant proteins are typically high-protein secreting mutant strains that have been selected a specific purpose, such as efficient cellulose-degrading enzymes. Somewhat surprisingly, sequencing genomes series cellulolytic Trichoderma reesei, widely an expression host gene products, has shed very little light on nature changes boost high-level protein secretion. While it is generally agreed and shown secretion in filamentous fungi occurs mainly through hyphal tip, there growing evidence also takes place sub-apical regions. Attempts to increase correct folding thereby yields heterologous fungal hosts by co-expression cellular chaperones foldases resulted variable success; underlying reasons explored at transcriptional level. The observed physiological experiencing increasing stress overexpression under strong promoters reflect challenge organisms experiencing. It evident, with other eukaryotes, ER highly dynamic structure. Considering above, emerging body work exploring use weaker avoid undue stress. Filamentous hailed candidates pharmaceutically relevant therapeutic use. One biggest challenges terms fungally-produced products their mode glycosylation; lack functionally important terminal sialylation glycans mammalian cells. Finally, exploration metabolic pathways fluxes together development sophisticated fermentation protocols may result new strategies produce fungi.