Genome shuffling is widely used for increasing the production of metabolites by bacterial strains, improving
substrate uptake as well as enhancing strain tolerance. This technique combines the advantage of multiparental
crossing allowed by DNA shuffling together with the recombination of entire genomes normally associated with
conventional breeding, or through protoplast fusion that increases the recombination process. The method of
genome shuffling was first presented by Stemmer and co-workers in 2002 when it was used to improve the
production of tylosin by Streptomyces fradiae. Nowadays, it is used in many experiments for increasing the
production of metabolites by bacterial strains, improving substrate uptake, and enhancing strain tolerance.
Genome shuffling is a major milestone in the strain-improvement technology and metabolic engineering.