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