A dicarboxylate/4-hydroxybutyrate autotrophic carbon assimilation cycle in the hyperthermophilic Archaeum Ignicoccus hospitalis.
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.
Huber
Harald
H
Lehrstuhl für Mikrobiologie und Archaeenzentrum, Universität Regensburg, Universitaetsstrasse 31, D-93053 Regensburg, Germany. harald.huber@biologie.uni-r.de
Gallenberger
Martin
M
Jahn
Ulrike
U
Eylert
Eva
E
Berg
Ivan A
IA
Kockelkorn
Daniel
D
Eisenreich
Wolfgang
W
Fuchs
Georg
G
D000105:Acetyl Coenzyme A / Q000096:biosynthesis*; D000596:Amino Acids / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism*; D002247:Carbon Isotopes / Q000032:analysis / Q000378:metabolism; D019620:Desulfurococcaceae / Q000378:metabolism*; D003998:Dicarboxylic Acids / Q000378:metabolism*; D006885:Hydroxybutyrates / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism; D019802:Succinic Acid / Q000378:metabolism
D000596:Amino Acids; D002247:Carbon Isotopes; D003998:Dicarboxylic Acids; D006885:Hydroxybutyrates; D011506:Proteins; D002245:Carbon Dioxide; C111420:4-hydroxybutyric acid; D000105:Acetyl Coenzyme A; D019289:Pyruvic Acid; D019802:Succinic Acid