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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.

SUBMITTER: Marcheschi RJ

PROVIDER: S-EPMC3571861 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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

Marcheschi Ryan J RJ Li Han H Zhang Kechun K Noey Elizabeth L EL Kim Seonah S Chaubey Asha A Houk K N KN Liao James C JC

ACS chemical biology 20120203 4

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, ...[more]

PMID: 22242720

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Project description:Carbon chain elongation (CCE), a reaction within the carboxylate platform that elongates short-chain to medium-chain carboxylates by mixed culture, has attracted worldwide interest. The present study provides insights into the microbial diversity and predictive microbial metabolic pathways of a mixed-culture CCE microbiome on the basis of a comparative analysis of the metagenome and metatranscriptome. We found that the microbial structure of an acclimated chain elongation microbiome was a highly similar to that of the original inoculating biogas reactor culture; however, the metabolic activities were completely different, demonstrating the high stability of the microbial structure and flexibility of its functions. Additionally, the fatty acid biosynthesis (FAB) pathway, rather than the well-known reverse β-oxidation (RBO) pathway for CCE, was more active and pivotal, though the FAB pathway had more steps and consumed more ATP, a phenomenon that has rarely been observed in previous CCE studies. A total of 91 draft genomes were reconstructed from the metagenomic reads, of which three were near completion (completeness, >97%) and were assigned to unknown strains of Methanolinea tarda, Bordetella avium, and Planctomycetaceae The last two strains are likely new-found active participators of CCE in the mixed culture. Finally, a conceptual framework of CCE, including both pathways and the potential participators, was proposed.IMPORTANCE Carbon chain elongation means the conversion of short-chain volatile fatty acids to medium-chain carboxylates, such as n-caproate and n-caprylate with electron donors under anaerobic condition. This bio-reaction can both expand the resource of valuable biochemicals and broaden the utilization of low-grade organic residues in a sustainable biorefinery context. Clostridium kluyveri is conventionally considered model microbe for carbon chain elongation which uses the reverse β-oxidation pathway. However, little is known about the detailed microbial structure and function of other abundant microorganism in a mixed culture (or open culture) of chain elongation. We conducted the comparative metagenomic and metatranscriptomic analysis of a chain elongation microbiome to throw light on the underlying functional microbes and alternative pathways.

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

Publications

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

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