Metabolite production from carbon dioxide using sugar catabolism in cyanobacteria has been in the spotlight recently. Synechocystis sp. PCC 6803 (Synechocystis 6803) is the most studied cyanobacterium for metabolite production. Previous in vivo analyses revealed that the oxidative pentose phosphate (OPP) pathway is at the core of sugar catabolism in Synechocystis 6803. However, the biochemical regulation of the OPP pathway enzymes in Synechocystis 6803 remains unknown. Therefore, we characterized a key enzyme of the OPP pathway, glucose-6-phosphate dehydrogenase (G6PDH), and related enzymes from Synechocystis 6803. Synechocystis 6803 G6PDH was inhibited by citrate in the oxidative tricarboxylic acid (TCA) cycle. Citrate has not been reported as an inhibitor of G6PDH before. Similarly, 6-phosphogluconate dehydrogenase, the other enzyme from Synechocystis 6803 that catalyzes the NADPH-generating reaction in the OPP pathway, was inhibited by citrate. To understand the physiological significance of this inhibition, we characterized succinic semialdehyde dehydrogenase (SSADH) from Synechocystis 6803 (SySSADH), which catalyzes one of the NAD(P)H generating reactions in the oxidative TCA cycle. Similar to isocitrate dehydrogenase from Synechocystis 6803, SySSADH specifically catalyzed the NADPH-generating reaction and was not inhibited by citrate. The activity of SySSADH was lower than that of other bacterial SSADHs. Previous and this studies revealed that unlike the OPP pathway, the oxidative TCA cycle is a pathway with low efficiency in NADPH generation in Synechocystis 6803. It has, thus, been suggested that to avoid NADPH overproduction, the OPP pathway dehydrogenase activity is repressed when the flow of the oxidative TCA cycle increases in Synechocystis 6803.
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Cover Image
Cover Image
Nanobodies reset the time of the bacterial LRRK2 cycle. A bacterial homologue of the Parkinson's disease (PD)-associated protein LRRK2 cycles between a dimeric and monomeric state concomitant with GTP binding and hydrolysis, and certain PD mutations disrupt this cycle by stabilizing the dimer. In this issue Leemans and co-workers (pp. 1203–1218) report the identification and characterization of a Nanobody that can allosterically modulate this GTPase cycle, thereby "resetting" the deregulating effect of PD mutations. The front image shows the structure of the bacterial LRRK2 that we previously solved in the background, with in the foreground the bacterial LRRK2 dimer/monomer cycle represented as a clock that is being reset by the Nanobody shown as the arrows of the clock hands. The image was created by Christian Galicia and provided by Wim Versées.
Unconventional biochemical regulation of the oxidative pentose phosphate pathway in the model cyanobacterium Synechocystis sp. PCC 6803
