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A Synthetic Recursive “+1” Pathway for Carbon Chain Elongation
journal contribution
posted on 2012-04-20, 00:00 authored by Ryan J. Marcheschi, Han Li, Kechun Zhang, Elizabeth L. Noey, Seonah Kim, Asha Chaubey, K. N. Houk, James C. LiaoNature uses four methods of carbon chain elongation for
the production
of 2-ketoacids, 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 involved in leucine 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-heptanol, 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.