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Curr Opin Chem Biol. 2008 Apr;12(2):168-76. doi: 10.1016/j.cbpa.2008.01.017. Epub 2008 Feb 29.

Combinatorial engineering of microbes for optimizing cellular phenotype.

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  • 1Department of Chemical Engineering, Massachusetts Institute of Technology, Room 56-469, Cambridge, MA 02139, United States.


Although random mutagenesis and screening and evolutionary engineering have long been the gold standards for strain improvement in industry, the development of more sophisticated recombinant DNA tools has led to the introduction of alternate methods for engineering strain diversity. Here, we summarize several combinatorial cell optimization methods developed in recent years, many of which are more amenable to phenotypic transfer and more efficient in probing greater dimensions of the available phenotypic space. They include tools that enable the fine-tuning of pathway expression (synthetic promoter libraries, tunable intergenic regions (TIGRs)), methods for generating randomized knockout and overexpression libraries, and more global techniques (artificial transcription factor engineering, global transcription machinery engineering, ribosome engineering, and genome shuffling) for eliciting complex, multigenic cellular properties.

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