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^*

来源：ACS Chemical Biology, 2012, 7(4): 689-697.

DOI：10.1021/cb200313e

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.

• 出版日期2012-4