Bridging the Gap Between Chemistry and Biotechnology - Large Molecules with Potential, How Could Biotechnology Complement Chemistry?

Chemical synthesis of small molecules is well established and enzyme-mediated chemical synthesis is a growing area, with great potential to be expanded in the future. The recombinant production of proteins has become routine. But molecules of intermediate size remain generally much more difficult to be produced in a sustainable way. Oligopeptides, oligosaccharides and oligonucleotides are three areas orphaned by biotechnology. The industrial manufacturing of all three oligomer types uses almost exclusively chemical synthesis, although conceptually biotechnological methods exist. This review gives an introduction to the market and applications of all three product classes as well as manufacturing options. The future situation could become difficult for all three, but particularly rapidly for peptides, where a number of products are discussed for markets other than the parenteral (injectable) pharmaceuticals. Cost and e-factors of actual chemical methods are by far too high to allow such commercial application, and ecologically and economically sustainable manufacturing methods are urgently needed. The review also shows that similar problems may arise for future pharmaceutical oligonucleotide and oligosaccharide drug products, as aspects of sustainability and cost of goods may significantly limit their broad availability and thereby their potential for commercial success.