The Entner-Doudoroff pathway is an overlooked glycolytic route in cyanobacteria and plants.
Glucose degradation pathways are central for energy and carbon metabolism throughout all domains of life. They provide ATP, NAD(P)H, and biosynthetic precursors for amino acids, nucleotides, and fatty acids. It is general knowledge that cyanobacteria and plants oxidize carbohydrates via glycolysis [the Embden-Meyerhof-Parnas (EMP) pathway] and the oxidative pentose phosphate (OPP) pathway. However, we found that both possess a third, previously overlooked pathway of glucose breakdown: the Entner-Doudoroff (ED) pathway. Its key enzyme, 2-keto-3-deoxygluconate-6-phosphate (KDPG) aldolase, is widespread in cyanobacteria, moss, fern, algae, and plants and is even more common among cyanobacteria than phosphofructokinase (PFK), the key enzyme of the EMP pathway. Active KDPG aldolases from the cyanobacterium Synechocystis and the plant barley (Hordeum vulgare) were biochemically characterized in vitro. KDPG, a metabolite unique to the ED pathway, was detected in both in vivo, indicating an active ED pathway. Phylogenetic analyses revealed that photosynthetic eukaryotes acquired KDPG aldolase from the cyanobacterial ancestors of plastids via endosymbiotic gene transfer. Several Synechocystis mutants in which key enzymes of all three glucose degradation pathways were knocked out indicate that the ED pathway is physiologically significant, especially under mixotrophic conditions (light and glucose) and under autotrophic conditions in a day/night cycle, which is probably the most common condition encountered in nature. The ED pathway has lower protein costs and ATP yields than the EMP pathway, in line with the observation that oxygenic photosynthesizers are nutrient-limited, rather than ATP-limited. Furthermore, the ED pathway does not generate futile cycles in organisms that fix CO2 via the Calvin-Benson cycle.
Department of Biology, Botanical Institute, Christian-Albrechts-University, 24118 Kiel, Germany;
Xi
X
Chen
Department of Biology, Botanical Institute, Christian-Albrechts-University, 24118 Kiel, Germany;
Karoline
K
Schreiber
Department of Biology, Botanical Institute, Christian-Albrechts-University, 24118 Kiel, Germany;
Jens
J
Appel
Department of Biology, Botanical Institute, Christian-Albrechts-University, 24118 Kiel, Germany;
Alexander
A
Makowka
Department of Biology, Botanical Institute, Christian-Albrechts-University, 24118 Kiel, Germany;
Berit
B
Fähnrich
Department of Biology, Institute of Molecular Evolution, Heinrich-Heine-University, 40225 Dusseldorf, Germany;
Mayo
M
Roettger
Department of Physiology and Cell Biology, Leibniz Institute of Plant Genetics and Crop Plant, 06466 Stadt Seeland, Gatersleben, Germany;
Mohammad R
MR
Hajirezaei
Department of Chemistry, Institute of Organic Chemistry, Christian-Albrechts-University, 24118 Kiel, Germany;
Frank D
FD
Sönnichsen
Department of Biology, Institute of Microbiology, Christian-Albrechts-University, 24118 Kiel, Germany.
Peter
P
Schönheit
Department of Biology, Institute of Molecular Evolution, Heinrich-Heine-University, 40225 Dusseldorf, Germany;
William F
WF
Martin
Department of Biology, Botanical Institute, Christian-Albrechts-University, 24118 Kiel, Germany; kgutekunst@bot.uni-kiel.de.
Kirstin
K
Gutekunst
D000446:Aldehyde-Lyases / Q000378:metabolism*; D000458:Cyanobacteria / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000502:physiology*; D008954:Models, Biological; D010944:Plants / Q000378:metabolism*; D019289:Pyruvic Acid / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D019289:Pyruvic Acid; D000446:Aldehyde-Lyases; C100131:phospho-2-keto-3-deoxy-gluconate aldolase; D005947:Glucose
Embden–Meyerhof–Parnas pathway; Entner–Doudoroff-pathway; endosymbiotic gene transfer; glucose degradation; oxidative pentose phosphate pathway