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m i c r o b i a l p h y s i o lo gy Five ways to cycle

Autotrophs participate in the carbon An inability to detect cycle by fixing to the regeneration of produce the biomass that all other acetyl-CoA from use for life. Four autotro- succinyl-CoA phic carbon-fixation pathways were during autotrophic already known and Berg et al. now growth of M. sedula led Fuchs report a fifth pathway that is used by and co-workers to propose a from diverse habitats. modified form of this pathway The best-known autotrophic in this . pathway is the Calvin–Bassham– Berg et al. tackled the Benson cycle, which is present in problem of how acetyl-CoA is plants, , and regenerated in M. sedula and . A second autotrophic other archaea and now report pathway (Arnon–Buchanan cycle) their results in Science. They detected uses a reductive cycle and formulated a working hypothesis and, subsequently, is found in anaerobic or microaero- that succinyl-CoA is reduced to purified. Using peptide sequences philic and archaea. A third 4‑hydoxybutyrate, which is then from these they detected autotrophic pathway (Wood– converted into two molecules of the cognate genes in the sequenced Ljungdahl pathway) uses a reductive acetyl‑CoA by 4-hydroxybutyryl- genome and used these gene acetyl-CoA pathway and is only CoA dehydratase, an ‑sensitive sequences to identify similar genes found in strictly anaerobic bacteria enzyme that they detected in the in other genomes. All of and archaea. A fourth pathway uses genomes of many of the autotrophic these autotrophic archaea are micro- the 3-hydroxypropionate cycle. archaea that have been sequenced aerophiles or anaerobes. The latest research builds on to date. Cell extracts of M. sedula Importantly, 189 partial or previous work from the Fuchs labo- catalysed the conversion of succinyl- complete 4-hydroxybutyryl-CoA ratory, which showed that enzyme CoA to 4-hydroxybutyrate in the dehydratase gene sequences were activities of the 3-hydroxypropio- presence of NADPH, and converted found after searching the Global nate cycle are upregulated during 4-hydroxybutyrate to acetyl-CoA if Ocean Sampling dataset; mesophilic autotrophic growth of the archaeon MgATP, CoA and NAD were sup- marine archaea that fix carbon by sedula, thereby sup- plied. They named this autotrophic this new pathway might make a con- porting a role for this cycle in carbon pathway the 3-hydroxypropio- siderable contribution to the global fixation. The first reaction in the nate/4-hydroxybutyrate assimilation . 3-hydroxypropionate carbon diox- pathway. Susan Jones ide-fixation cycle is the When M. sedula was grown on Original Research Paper of acetyl-CoA; the carbon dioxide a mixture of , oxygen and Berg, I. A., Kockelhorn, D., Buckel, W. & Fuchs, G. acceptor is then regenerated in a carbon dioxide, the enzymes that A 3‑hydroxypropionate/4‑hydroxybutyrate cyclic process, with 3-hydroxypropio- are required for the conversion of autotrophic carbon dioxide assimilation pathway in archaea. Science 318, 1782–1786 (2007) nate and malyl-CoA as intermediates. succinyl-CoA to acetyl-CoA were

nature reviews | microbiology volume 6 | february 2008 © 2008 Nature Publishing Group