Question

Select the incorrect statement about the insulin hormone produced by rDNA technique.

• A. Two DNA sequences corresponding to A and B chains of insulin were prepared and introduced in E. coli.
• B. Chains A and B were produced separately.
• C. Two chains were extracted and combined with C chain.
• D. In 1983, Eli Lilly, an American company, prepared the first human insulin.

Hint:

Production of Humulin:
$\bullet$ Proinsulin = A chain + B chain + C peptide.
$\bullet$ Mature functional insulin = A chain + B chain (joined by disulfide bonds, NO C-peptide).
$\bullet$ Eli Lilly produced Chains A and B separately in E. coli and joined them via disulfide bridges.

Answer 1

The Correct Option is C

Concept:
Human insulin consists of two short polypeptide chains: Chain A (21 amino acids) and Chain B (30 amino acids) linked together by disulfide bonds. Synthesizing active human insulin via rDNA required bypassing proinsulin processing.

Step 1: Biotechnology of Humulin Production (Eli Lilly, 1983):
In humans, insulin is synthesized as a pro-hormone containing an extra C-peptide (connecting peptide) of 33 amino acids that is cleaved during maturation to yield mature insulin.
Because E. coli cannot process eukaryotic proinsulin properly, the American pharmaceutical company Eli Lilly (1983) devised an innovative strategy:
1. They chemically synthesized two separate DNA oligonucleotide sequences corresponding to Chain A and Chain B of human insulin.
2. These sequences were inserted into plasmids and introduced into E. coli hosts to express Chain A and Chain B separately.
3. The individual A and B chains were extracted, purified, and then combined in vitro by creating disulfide bonds to produce mature, functional human insulin (Humulin).
4. The C chain is not added during the synthesis of mature recombinant insulin; mature insulin completely lacks the C-peptide.

Step 2: Analysis of the Statements:
- Statements (A), (B), and (D) are factually correct.
- Statement (C) is incorrect because chains A and B are linked by disulfide bonds, not combined with the C chain.

Step 3: Final Answer:
Hence, Option (C) is the incorrect statement.