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A Synthetic Recursive "+1" Pathway for Carbon Chain Elongation

  作者 MARCHESCHI RYAN J; LI HAN; ZHANG KECHUN; NOEY ELIZABETH L; KIM SEONAH; CHAUBEY ASHA; HOUK K N; LIAO JAMES C  
  选自 期刊  ACS CHEMICAL BIOLOGY;  卷期  2012年7-4;  页码  689-697  
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[摘要]Nature uses four methods of carbon chain elongation for the production of 2-ketoacid, fatty acids, polyketides, and isoprenoids. Using a combination of quantum mechanical (QM) modeling protein-substrate modeling, and protein and metabolic engineering, we have engineered the enzymes involed in leuchine biosynthesis for use as a synthetic "+1" recursive metabolic pathway to extend the carbon chain of 2-ketoacids. This modified pathway preferentially selects longer-chain substrates for catalysis, as compared to the non-recursive natural pathway, and can recursively catalyze five elongation cycles to synthesize bulk chemicals, such as 1-octanol, and phenylpropanol directly from glucose. The +1 chemistry is a valuable metabolic tool in addition to the "+5" chemistry and "+2" chemistry for the biosynthesis of isoprenoids, fatty acids, or polyketides.

 
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