In this project Innophore works together with c-LEcta (Leipzig, Germany) and other industrial partners.
The goal is to discover new glycosyltranferases and to use them commercially.
Innophore with their Catalophore platform has an extremely innovative approach, using in-silico methods focusing only on active site cavities of enzymes.
Selective glycosylation – the attachment of carbohydrate units to organic compounds or other sugars – is an effective strategy that nature takes to expand the biological information of biomolecules. Several glycosylated compounds turned out to be very attractive products for food and nutrition, pharma, cosmetics and other industries. They cover the range from the complex human milk oligosaccharides (HMO), prebiotics like galactooligosaccharides (GOS) etc. to glycosylated therapeutic proteins and many other products. However, specific glycosylation is by chemical means a very complicated and expensive synthesis method. A solution is the application of selective enzymes for the formation of specific carbohydrate linkages.
The enzyme class that is most versatile for the formation of carbohydrate linkages are glycosyltransferases (GTs, 1-2% of all gene products are GTs in all kingdoms of life distributed over only two relevant folding classes)1. They utilize mono- or diphosphonucleotide activated sugars like UDP-glucose (UDP-Glc). For the industrial application of these donors, they need to be recycled in the process due to their high price and inhibitory effect. A cell free process with recycling of UDP-Glc has already been developed by c-LEcta and is today applied in industrial scale synthesis processes.
Glycosyltransferases often show high selectivity and high activities. The general problems are the identification of glycosyltransferases with high affinity to the substrate, the correct selectivity for the glycosylation as well as the often difficult recombinant expression of the mostly eukaryotic genes in E. coli. We are going to address these issues by the application of modern bioinformatic tools. Automated analysis of enzyme structures should identify enzymes accepting certain target substrates or predict the possible substrate scope of identified enzymes.
The identified GTs shall be applied in processes to synthesize glycosylated products. A set of target compounds will be selected and the reactions will be optimized to access pure products. Thus, the project will yield a platform of enzymes, synthetic procedures and finally also glycosylated products for exploitation.
1 Lairson et al., Annu. Rev. Biochem. 2008, 77, 521-555