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1: Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7851-6. Epub 2008 May 29.
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A dicarboxylate/4-hydroxybutyrate autotrophic carbon assimilation cycle in the hyperthermophilic Archaeum Ignicoccus hospitalis.

Huber H, Gallenberger M, Jahn U, Eylert E, Berg IA, Kockelkorn D, Eisenreich W, Fuchs G.

Lehrstuhl für Mikrobiologie und Archaeenzentrum, Universität Regensburg, Universitaetsstrasse 31, D-93053 Regensburg, Germany. harald.huber@biologie.uni-r.de

Ignicoccus hospitalis is an anaerobic, autotrophic, hyperthermophilic Archaeum that serves as a host for the symbiotic/parasitic Archaeum Nanoarchaeum equitans. It uses a yet unsolved autotrophic CO(2) fixation pathway that starts from acetyl-CoA (CoA), which is reductively carboxylated to pyruvate. Pyruvate is converted to phosphoenol-pyruvate (PEP), from which glucogenesis as well as oxaloacetate formation branch off. Here, we present the complete metabolic cycle by which the primary CO(2) acceptor molecule acetyl-CoA is regenerated. Oxaloacetate is reduced to succinyl-CoA by an incomplete reductive citric acid cycle lacking 2-oxoglutarate dehydrogenase or synthase. Succinyl-CoA is reduced to 4-hydroxybutyrate, which is then activated to the CoA thioester. By using the radical enzyme 4-hydroxybutyryl-CoA dehydratase, 4-hydroxybutyryl-CoA is dehydrated to crotonyl-CoA. Finally, beta-oxidation of crotonyl-CoA leads to two molecules of acetyl-CoA. Thus, the cyclic pathway forms an extra molecule of acetyl-CoA, with pyruvate synthase and PEP carboxylase as the carboxylating enzymes. The proposal is based on in vitro transformation of 4-hydroxybutyrate, detection of all enzyme activities, and in vivo-labeling experiments using [1-(14)C]4-hydroxybutyrate, [1,4-(13)C(2)], [U-(13)C(4)]succinate, or [1-(13)C]pyruvate as tracers. The pathway is termed the dicarboxylate/4-hydroxybutyrate cycle. It combines anaerobic metabolic modules to a straightforward and efficient CO(2) fixation mechanism.

Publication Types:
PMID: 18511565 [PubMed - indexed for MEDLINE]

PMCID: PMC2409403 [Available on 12/03/08]