A synthetic recursive "+1" pathway for carbon chain elongation.

Abstract:

:Nature 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.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Marcheschi RJ,Li H,Zhang K,Noey EL,Kim S,Chaubey A,Houk KN,Liao JC

doi

10.1021/cb200313e

subject

Has Abstract

pub_date

2012-04-20 00:00:00

pages

689-97

issue

4

eissn

1554-8929

issn

1554-8937

journal_volume

7

pub_type

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