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BioTechnology QUESTION #10595
Question 1
L-Lysine overproduction in C. glutamicum is achieved by deregulating the aspartate pathway. A key mutation required is:
  • Deletion of the aconitase gene to block the TCA cycle
  • A feedback-insensitive (desensitised) aspartokinase that is no longer inhibited by lysine + threonine✔️
  • Overexpression of the glutamate dehydrogenase gene
  • Introduction of a heterologous arginine biosynthesis pathway
Correct Answer Explanation
In wild-type C. glutamicum, aspartokinase is subject to concerted feedback inhibition by both lysine AND threonine simultaneously. Mutations creating a feedback-insensitive aspartokinase allow carbon flux to continue through the aspartate pathway even when lysine accumulates. Additional engineering includes deletion of competing branches (homoserine dehydrogenase to block threonine synthesis), amplifying lysine-specific enzymes. This rational metabolic engineering produces >100 g/L lysine.