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Centre for Extremophile Research

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Central Metabolism in the Archaea

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Staff - Dr David Hough, Prof. Michael Danson.

The pathways of central metabolism provide the metabolic connections between the catabolic (degradative) and anabolic (biosynthetic) routes in all living organisms. In hyperthermophilic Archea, we have discovered a promiscuous central metabolic pathway that catabolizes a variety of sugars using a single set of enzymes. Most organisms catabolize hexose sugars to pyruvate with a net generation of ATP via substrate level phosphorylation. Two thermoacidophiles, Sulfolobus and Thermoplasma, are able to metabolize D-glucose via a non-phosphorylative variant of the Entner-Doudoroff pathway leading to no net production of ATP. This rare 'promiscuous metabolic pathway' was discovered at the CER. We explored the structural basis of this promiscuity in these enzymes that have to maintain their integrity at temperatures approaching 100oC. The determination of the 3-D structure of Sulfolobus 2-keto-3-deoxygluconate aldolase (KDGA) showed how the active site can bind both KDGlu and KDGal complexes, yielding pyruvate and glyceraldehyde in both cases. As a result of this promiscuity, the enzyme unusually exhibits no stereocontrol in biocatalysis.

KDGA active site with both substrates bound.
Aldolase + KD-galactonate
Aldolase + KD-gluconate

 

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