Engineering genomes in multiplex

Efficiently engineering robust complex traits is a key challenge facing metabolic engineering efforts to synthesize valuable products in vivo. Recent advances in genome engineering confront this barrier and significantly enhance the ability to map functional changes targeted throughout the genome and combinatorially optimize complex (multigenic) traits using multiplex recombineering. We describe a framework for efficiently searching genome-wide combinatorial space to optimize complex traits and highlight recent advances in genome engineering that enable this approach.

► An algorithm for genome engineering of complex traits is presented.
► To efficiently search for trait-conferring mutations, targeted, functional mutations should be used to introduce genetic diversity.
► Combinatorial optimization on the genome-scale requires narrowing to relevant genetic targets to efficiently search the genotypic space.
► We review advances in multiplex recombineering and their application to genome engineering.