TuP-08



GLYCOSYLATION OF CELLOBIOHYDROLASE I FROM TRICHODERMA REESEI

Amanda Nouwens, Daniel Jardine, Natasha Zachara, Nicolle Packer, Helena Nevalainen

Macquarie University Centre for Analytical Biotechnology
Macquarie University, Sydney, NSW, 2109



Trichoderma reesei is a filamentous fungus that can secrete cellulose-degrading enzymes (cellulases) in high yields. The importance of cellulases commercially and environmentally has provoked an interest in their structure and function. The potential of T. reesei as a production host for non-fungal proteins has led to an interest in port-translational modifications, particularly glycosylation and the authenticity of heterologous proteins.

Cellobiohydrolase I (CBH I), an exocellulase, comprises over 50% of the secreted protein produced by T. reesei when grown in the presence of cellulose homologues. The amino acid sequence suggests there are four potential N-glycosylation sites and a spacer region with many potential sites for O-glycosylation. The extent of glycosylation is not well characterized and may vary due to substrate and growth conditions. The importance of glycosylation for crystallisation studies of CBH I, authenticity of heterologous proteins and enzyme activity has resulted in a need for characterization of this protein produced under industrial fermentation conditions.

A previous purified sample of CBH from a genetically engineered strain of Trichoderma reesei grown on lactose was available for characterization. Isoelectrofocussing (IEF) electrophoresis showed the presence of six isoforms. Monosaccharide analysis of CBH I indicated the presence of mannose, glucose and glucosamine.

The CBH I protein was digested with trypsin and trypsin/PNGase F in order to characterize the glycosylation sites. Glycopeptides were identified using LC/MS and LC/MS/MS by monitoring the collision induced fragments produced from the carbohydrate residues. Sequencing of the LC/MS identified glycopeptides on a Beckman GlycoSite solid-phase sequencer and subsequent confirmation by MS/MS indicated the presence of unusual N-linked glycosylations in the form of a single N-acetylglucosamine residue at least two of the potential N-linked sites. It also appears that PNGase F only partially removes this single sugar.

The occurrence of the single N-linked N-acetylglucosamine residues may be due to the functional requirements of the protein for secretion outside the organism.