Current trends in biopharmaceuticals production in Escherichia coli.

Since the manufacture of the first biotech product for a fledgling biopharmaceutical industry in 1982, Escherichia coli, has played an important role in the industrial production of recombinant proteins. It is now 40 years since the introduction of Humulin® for the treatment of diabetes. E. coli remains an important production host, its use as a cell factory is well established and it has become the most popular expression platform particularly for non-glycosylated therapeutic proteins. A number of significant inherent obstacles in the use of prokaryotic expression systems to produce biologics has always restricted production. These include codon usage, the absence of post-translational modifications and proteolytic processing at the cell envelope. In this review, we reflect on the contribution that this model organism has made in the production of new biotech products for human medicine. This will include new advancements in the E. coli expression system to meet the biotechnology industry requirements, such as novel engineered strains to glycosylate heterologous proteins, add disulphide bonds and express complex proteins. The biopharmaceutical market is growing rapidly, with two production systems competing for market dominance: mammalian cells and microorganisms. In the past 10 years, with increased growth of antibody-based therapies, mammalian hosts particularly CHO cells have dominated. However, with new antibody like scaffolds and mimetics emerging as future proteins of interest, E. coli has again the opportunity to be the selected as the production system of choice.