Figure 9.17 shows three posttranslational steps required to produce the sugar-regulating hormone insulin from the starting polypeptide product preproinsulin.

Explain why it is not feasible to insert the entire human insulin gene into E. coli and anticipate the production of insulin.

Key Concepts

Posttranslational Modifications

Posttranslational modifications are chemical changes that occur to a protein after its synthesis, which are crucial for its functionality. In the case of insulin, these modifications include the cleavage of the preproinsulin precursor into proinsulin and then into active insulin, as well as the formation of disulfide bonds. E. coli lacks the necessary cellular machinery to perform these specific modifications, making it unable to produce functional insulin from the inserted gene.

Gene Expression in Prokaryotes vs. Eukaryotes

Gene expression mechanisms differ significantly between prokaryotes, like E. coli, and eukaryotes, such as humans. Eukaryotic genes often contain introns that must be spliced out to produce a functional mRNA, while prokaryotic systems do not have introns. If the entire human insulin gene, which includes introns, is inserted into E. coli, the bacteria will not be able to process the gene correctly, leading to the production of non-functional proteins.

Protein Folding and Function

Proper protein folding is essential for the biological activity of proteins, including hormones like insulin. The folding process is influenced by the protein's amino acid sequence and the cellular environment. E. coli may not provide the correct conditions or chaperone proteins necessary for insulin to fold into its active conformation, resulting in misfolded or inactive insulin, which cannot perform its regulatory functions in glucose metabolism.