Document Detail


A synthetic recursive "+1" pathway for carbon chain elongation.
MedLine Citation:
PMID:  22242720     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Ryan J Marcheschi; Han Li; Kechun Zhang; Elizabeth L Noey; Seonah Kim; Asha Chaubey; K N Houk; James C Liao
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-02-03
Journal Detail:
Title:  ACS chemical biology     Volume:  7     ISSN:  1554-8937     ISO Abbreviation:  ACS Chem. Biol.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-20     Completed Date:  2012-10-19     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101282906     Medline TA:  ACS Chem Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  689-97     Citation Subset:  IM    
Affiliation:
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, United States.
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MeSH Terms
Descriptor/Qualifier:
Carbon / chemistry*
Fatty Acids / chemical synthesis*
Keto Acids
Metabolic Engineering*
Terpenes
Grant Support
ID/Acronym/Agency:
F32 GM099277/GM/NIGMS NIH HHS; GM36700/GM/NIGMS NIH HHS; R01 GM036700/GM/NIGMS NIH HHS; T32GM008496/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Fatty Acids; 0/Keto Acids; 0/Terpenes; 7440-44-0/Carbon
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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