Feedback inhibition evolution

As yet the biological rationale for the evolution of the groups of slightly different compounds is not known. Modification of the basic molecular structure may overcome feedback inhibition of the earlier enzymes or make adaptation to secondary products used as repellents more difficult. It seems most likely, however, that modifications are neutral to selection pressure and reflect the accumulation of random mutations (E). 

Feedback inhibition can be limited by optimizing both upstream and downstream enzyme expression such that the inhibitor does not significantly accumulate. In instances where a metabolite inhibits an enzyme in the isoflavonoid pathway, enzyme mutagenesis can alter the structural interaction between the enzyme and its inhibitor to block the inhibition mechanism. Recently, allosteric feedback inhibition of a tomato peel 4CL by naringenin 23, a product several steps downstream, was significantly reduced through directed evolution in E. coli [181]. 

Alberstein M, Eisenstein M, AbeliovichH (2012) Removing allosteric feedback inhibition of tomato 4-coumarate CoA ligase by directed evolution. Plant J 69 57-69... 

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