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Combinatorial engineering of microbes for optimizing cellular phenotype.

Christine Nicole S Santos¹, Gregory Stephanopoulos

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

Current Opinion in Chemical Biology

|February 16, 2008

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New recombinant DNA tools offer advanced methods for strain improvement beyond traditional techniques. These combinatorial cell optimization strategies efficiently explore cellular diversity for industrial applications.

Area of Science:

Synthetic biology
Metabolic engineering
Strain development

Background:

Traditional strain improvement relies on random mutagenesis and evolutionary engineering.
Advancements in recombinant DNA technology enable novel approaches for engineering cellular diversity.

Purpose of the Study:

To summarize recent combinatorial cell optimization methods.
To highlight techniques superior to traditional methods for probing phenotypic space.

Main Methods:

Fine-tuning pathway expression using synthetic promoter libraries and tunable intergenic regions (TIGRs).
Generating randomized knockout and overexpression libraries.
Employing global techniques like artificial transcription factor engineering, global transcription machinery engineering, ribosome engineering, and genome shuffling.

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Main Results:

These methods offer improved phenotypic transfer capabilities.
They are more efficient in exploring vast phenotypic spaces.
Enables elicitation of complex, multigenic cellular properties.

Conclusions:

Combinatorial cell optimization represents a significant advancement in industrial strain improvement.
These sophisticated methods provide greater efficiency and broader exploration of cellular potential.
They offer powerful alternatives to established strain engineering techniques.