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#pathway analysis

2 public questions tagged with this topic.

In a pathway A→B→C→D, if enzyme B is knocked out and enzyme C is overexpressed, growth requires

In pathway A→B→C→D where enzymes named for products knockout of early enzyme B prevents synthesis of B and consequently substrate for downstream steps C and D. Overexpressing enzyme C converting C to D cannot rescue because substrate C never produced; pathway remains blocked upstream despite increased catalytic potential downstream. No endogenous downstream intermediates exist to drive flux so cell auxotrophic. Only complete medium supplying final product D plus all other growth factors bypasses entire endogenous biosynthesis restoring growth. This illustrates epistasis of early block over lat

Ref: Griffiths et al., Introduction to Genetic Analysis, 12th ed., Chapter 14: Pathway Block Epistasis Over Overexpression Rescue

In pathway analysis, mutants blocked earlier require

Position of block predicts number of supplements capable of restoring growth due to sequential dependency of pathway. Early lesion abolishes synthesis of many downstream metabolites so exogenous provision of any compound beyond block including numerous intermediates and final product rescues prototrophy. Late lesion removes only final conversion so fewer compounds suffice for rescue. Consequently mutants blocked nearer start show broader supplementation requirement pattern while those near end need narrow rescue. Scoring breadth of positive growth therefore informs ordering of genes along bios

Ref: Snustad & Simmons, Principles of Genetics, 7th ed., Chapter 14: Auxotroph Rescue Breadth Reflects Block Position