Thermostable Nucleotide-Sugar Synthesizing Enzymes: Opportunity and Future Applications in Therapeutic Antibody and Peptide Area

Since discovery of the first antibiotic, penicillin, at 1928 by Sir Alexander Fleming from Penicillium notatum, many antibiotics were isolated from different types of microorganisms including molds and bacteria, especially actinomycetes. At present, medicines dominantly used are chemical compounds with low molecular weight, including antibiotics, however, it has been often observed that some of them cause serious side effects or damages to patients. Therefore, recently it has been attempted to develop antibody or peptide as medicine, because of their high specificity to target for avoiding unexpected side effect. However, problem to be solved on therapeutic antibody is shortage of its lifetime in the human circulatory system. To overcome this drawback, it is effective to add polysaccharide on these molecules. Conversely, the polymer structure of carbohydrate is known to work as a key molecule in the immune system; e.g. human histo-blood type is determined by only one sugar molecule at the terminal of long polysaccharide. For pharmacological and immunological demands, it is expected to add personal-specific polymer structure of carbohydrate molecules on antibody or peptide molecules. For construction of polysaccharide, many different types of glycosyltransferases were already identified from many different organisms, however, these enzymes can utilize only nucleotide-sugar molecules as substrate. Therefore, efficient and on-time supply of appropriate nucleotide-sugar molecule as substrate should be helpful in development of personalized and optimized utilization of therapeutic antibody or peptide. In this chapter, we will overlook enzymes with construction activity of nucleotide-sugar molecules and indicate opportunity on future application of these enzymes.