1. A method for altering an endonuclease recognition site specificity, comprising: (a) subjecting a mutagenized endonuclease gene library to a genetic selection in a population of prokaryotic host cells expressing one or more non-cognate DNA methyltransferases, wherein the genetic selection selects for viable cells in the population; and (b) identifying whether the viable cells express an active mutated endonuclease with an altered recognition site specificity.