# DBT JRF 2022 — Question 106

Exam: DBT JRF 2022 · Section: B · Topic: Industrial Microbiology › Strain Improvement by Mutagenesis · Difficulty: Medium

## Question

Penicillin titers have been increased more than 1000 fold by classical mutagenesis from the original Fleming strain. The reason behind this increase in the titer is:

## Options

- **A.** Increase in the promoter strength of the penicillin encoding genes
- **B.** Increase in the stability of the mRNA of these genes
- **C.** Increase in the stability of the proteins encoded by these genes
- **D.** Removal of the regulatory controls in the penicillin pathway

## Answer

Option D

## Explanation

Penicillin titer improvement — removal of feedback regulation: Classical mutagenesis and strain improvement of Penicillium chrysogenum over decades achieved >1000-fold improvement in penicillin yield. Primary mechanism: REMOVAL OF FEEDBACK REGULATORY CONTROLS: • Wild-type Penicillium has feedback inhibition and catabolite repression of penicillin biosynthetic genes (pcbAB, pcbC, penDE). • Accumulated penicillin or pathway intermediates feed back to inhibit their own synthesis. • Mutant strains selected for high penicillin production typically have mutations that release these feedback controls, allowing constitutive overexpression of biosynthetic genes. • Additionally: gene amplification of biosynthetic clusters, improved precursor supply (phenylacetic acid), and enhanced secretion. Other factors contributing: more efficient secretion, reduced degradation, but the MAJOR reason is loss of feedback regulation. Answer: >1000-fold improvement in penicillin titer is primarily due to removal of feedback inhibition on the biosynthetic pathway.

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