Cell factories for insulin production

Abstract

The rapid increase in the number of diabetic patients globally and exploration of alternate insulin delivery methods such as inhalation or oral route that rely on higher doses, is bound to escalate the demand for recombinant insulin in near future. Current manufacturing technologies would be unable to meet the growing demand of affordable insulin due to limitation in production capacity and high production cost. Manufacturing of therapeutic recombinant proteins require an appropriate host organism with efficient machinery for posttranslational modifications and protein refolding. Recombinant human insulin has been produced predominantly using E. coli and Saccharomyces cerevisiae for therapeutic use in human. We would focus in this review, on various approaches that can be exploited to increase the production of a biologically active insulin and its analogues in E. coli and yeast. Transgenic plants are also very attractive expression system, which can be exploited to produce insulin in large quantities for therapeutic use in human. Plant-based expression system hold tremendous potential for high-capacity production of insulin in very cost-effective manner. Very high level of expression of biologically active proinsulin in seeds or leaves with long-term stability, offers a low-cost technology for both injectable as well as oral delivery of proinsulin.

Chemically Precise Glycoengineering Improves Human Insulin

“…Unglycosylated insulin is commonly obtained via recombinant protein expression 34,35 in part because its chemical synthesis is unusually challenging. 36–39 Further complicating matters, to our knowledge, the total synthesis of glycosylated insulin has not been reported.…”

Plant Molecular Farming: Much More than Medicines

“…The benefits offered by plants as expression hosts are highlighted in several recent reports containing favorable head-to-head comparisons with other platforms (11)(12)(13). One of the key advantages of all plant-based systems is that plants are much less expensive than mammalian cells but have a similar secretory pathway.…”

The growing impact of lyophilized cell-free protein expression systems

“…1 The original workhorse of custom recombinant protein synthesis is Escherichia coli, which remains the most cost-effective method and can produce many complex proteins (including insulin 2 and antibodies 3 ). Other synthesis chassis including yeast and mammalian cells have been developed for proteins requiring advanced assembly and post-translational modifications such as glycosylation and lipidation.…”