Genome shuffling leads to rapid phenotypic improvement in bacteria

Ying-Xin Zhang, Kim Perry, Victor A. Vinci, Keith Powell, Willem P. C. Stemmer and Stephen B. del Cardayré ()
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Ying-Xin Zhang: Maxygen
Kim Perry: Maxygen
Victor A. Vinci: Eli Lilly and Company, Lilly Corporate Center
Keith Powell: Maxygen
Willem P. C. Stemmer: Maxygen
Stephen B. del Cardayré: Maxygen

Nature, 2002, vol. 415, issue 6872, 644-646

Abstract: Abstract For millennia, selective breeding, on the basis of biparental mating, has led to the successful improvement of plants and animals to meet societal needs1. At a molecular level, DNA shuffling mimics, yet accelerates, evolutionary processes, and allows the breeding and improvement of individual genes and subgenomic DNA fragments. We describe here whole-genome shuffling; a process that combines the advantage of multi-parental crossing allowed by DNA shuffling with the recombination of entire genomes normally associated with conventional breeding. We show that recursive genomic recombination within a population of bacteria can efficiently generate combinatorial libraries of new strains. When applied to a population of phenotypically selected bacteria, many of these new strains show marked improvements in the selected phenotype. We demonstrate the use of this approach through the rapid improvement of tylosin production from Streptomyces fradiae. This approach has the potential to facilitate cell and metabolic engineering and provide a non-recombinant alternative to the rapid production of improved organisms.

Date: 2002
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DOI: 10.1038/415644a

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