Strain improvement has traditionally been carried out by random mutagenesis and selection. Random mutagenesis is a relatively simple way to make many changes to an organism's genome, which in rare cases results in improved production in a desired process. However, these techniques do little to increase knowledge about what changes are beneficial and traditionally improved cells often have weak constitutions due to high mutational loads. In contrast, recombinant DNA techniques have been developed which involve the prediction and construction of single genetic changes to improve cell traits. These methods are often successful at engineering simple traits that can be predicted. However, they often fail to engineer traits that require multiple unanticipated genetic modifications, such as improved growth in a harsh industrial environment. We are developing a method called Trackable Recursive Multiplex Recombineering (TReMR) that combines the power of i) classical strain improvements ability to combine multiple beneficial mutations into a single host, and ii) recombinant DNA technologies ability to make genetic perturbations that are robust and easily identified by DNA microarray. The TReMR method is a two-step process of creating a genome-wide combinatorial library of rationally engineered E. coli mutants followed by selection of cells with improved phenotypes. This process will be carried out successively and all genetic changes that confer cells with superior traits will be easily identified.