| As the biotechnology industry matures, recombinant proteins are increasingly being used as commercially valuable therapeutics. The choice of recombinant host for manufacturing significantly affects protein production costs. Expression of recombinant proteins in insect cells through baculovirus expression vectors has advantages including culture cost, protein yields, and post-translational modifications. However, protein aggregation and the lack of complex glycosylation are disadvantages of the baculovirus expression system. The advent of high throughput DNA sequencing coupled with computer analysis has allowed the identification of novel proteins from many species, and some of these newly characterized enzymes may help overcome the limitations of the baculovirus system. For instance, the enzymes of the human signal peptidase complex have been identified based on homology to their canine counterparts and have been expressed in insect cells.; A more comprehensive example is the metabolic engineering of the sialic acid pathway into insect cells for the purpose of producing sialylated glycoproteins. Novel human genes encoding sialic acid enzymes have been identified based on homology with species as disparate as bacteria, and sialic acid metabolic pathways have been reconstructed in insect cells through the recombinant expression of the human enzymes. Furthermore, the pathways can produce different sialic acids in parallel, and their relative amounts can be controlled by altering cell culture conditions. These results not only suggest the possibility of producing sialylated glycoproteins in insect cells, but also the possibility of controlling the type of sialic acid. Ultimately, sialylation in insect cells may result by controlling their native machinery as work on the recently released Drosophila genome suggests the existence of sialic acid metabolism in at least some insect species. |
