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A synthetic recursive "+1" pathway for carbon chain elongation
Ryan J Marcheschi1, Han Li, Kechun Zhang
1Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, United States.
ACS Chemical Biology
|January 17, 2012
Summary
Researchers engineered a novel metabolic pathway for extending carbon chains in 2-ketoacids. This synthetic "+1" recursive pathway efficiently produces bulk chemicals like alcohols directly from glucose.
Area of Science:
- Metabolic Engineering
- Synthetic Biology
- Biocatalysis
Background:
- Nature employs diverse carbon chain elongation strategies for synthesizing essential molecules.
- Existing metabolic pathways have limitations in efficiently extending carbon chains for bulk chemical production.
Purpose of the Study:
- To engineer a synthetic metabolic pathway for recursive carbon chain elongation of 2-ketoacids.
- To develop a novel biocatalytic method for producing bulk chemicals from glucose.
Main Methods:
- Utilized quantum mechanical (QM) modeling and protein-substrate modeling.
- Employed protein and metabolic engineering to modify leucine biosynthesis enzymes.
- Established a recursive metabolic pathway for carbon chain extension.
Main Results:
- Engineered enzymes function as a synthetic "+1" recursive metabolic pathway.
- The modified pathway exhibits preferential selection for longer-chain substrates.
- Achieved five recursive elongation cycles to synthesize 1-heptanol, 1-octanol, and phenylpropanol from glucose.
Conclusions:
- The synthetic "+1" recursive pathway is a valuable metabolic tool.
- This approach complements existing "+2" and "+5" chemistries for biosynthesis.
- Enables direct production of bulk chemicals from simple sugars.
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