Again, let's consider the pathway W --> X --> Y --> Z, catalyzed by the enzymes A, B, and C in that order. The cell needs compound Z in order to replicate. Normally, you feed compound W to the cells, and enzymes A, B, and C convert compound W to compound Z, allowing the cell to survive. If any of enzymes A, B, or C are mutated and non-functional, the cell can no longer produce compound Z and the cells will not survive.
Let's say enzyme B (which catalyzes the conversion of compound X to compound Y) is mutated. If you feed the cells compound W, will the cell still be able to produce compound Z? If you feed the cells compound X, will the cells still be able to produce compound Z? If you feed the cells compound Y, will the cells still be able to produce compound Z?