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Dr Zhang Wei (left) conceived and designed project, Dr Siew Yin Yin (right) designed and conducted experiments, and Dr Dave Ow (middle) contributed to insulin production.

Science

Insulin is a lifesaver for patients with type 1 diabetes and an essential therapy for many with type 2 diabetes. According to WHO, more than 420 million people (6% of the world’s population) are living with diabetes. In Singapore, 8.6% of residents are suffering from diabetes, and estimated 19,000 more people are diagnosed diabetes every year. Hence, there is high demand for affordable insulin therapeutics. The studies we have done will help to develop a more efficient and economical process for insulin production.

Societal Impact

Purification process is one of the major bottlenecks in the production of insulin therapeutics. The study the team provides a cost-effective alternative approach to produce recombinant human insulin in a scalable and affordable manner. This may potentially help to address the current great unmet need for affordable insulin, especially in low- and middle-income nations.

Technical Summary

A new and efficient purification process for recombinant human insulin production from Escherichia coli was developed. The study explored new resins and optimized all purification steps from inclusion body washing to insulin polishing. The developed process has drastically improved the efficiency of inclusion body wash by introducing combined additives. Proinsulin recovery was increased by three-fold with the optimized solubilization and sulfitolysis design. A higher recovery and purity of proinsulin was achieved with high binding capacity cation exchange resin (CEX) compared to a reported process using costly affinity chromatography resin. Another CEX chromatography was applied to purify insulin as it offers better cost- and process-efficiency than reversed-phase chromatography that is commonly practiced. Cost-effectiveness and environmental sustainability were also improved by the reduction of organic solvent (ethanol) used in this process. This established process produces recombinant human insulin of over 98% purity, that is comparable to the reference standard.

Figure 1. Generic workflow for insulin produced from E. Coli

References

New and Efficient Purification Process for Recombinant Human Insulin Produced in Escherichia coli. Appl Microbiol Biotechnol. 2021;105(24):9137-9151. doi: 10.1007/s00253-021-11697-x.