AbstractPhosphoketolase (PKET) pathway is predominant in cyanobacteria (around 98%) but current opinion is that it is virtually inactive under autotrophic ambient CO2 condition (AC-auto). This creates an evolutionary paradox due to the existence of PKET pathway in obligatory photoautotrophs. We aim to answer the paradox with the aid of bioinformatic analysis along with metabolic, transcriptomic, fluxomic and mutant data integrated into a multi-level kinetic model. We discussed the problems linked to neglected isozyme, pket2 (sll0529) and inconsistencies towards the explanation of residual flux via PKET pathway in the case of silenced pket1 (slr0453) in Synechocystis sp. PCC 6803. Our in silico analysis showed: (1) 17% flux reduction via RuBisCO for Δpket1 under AC-auto, (2) 11.2–14.3% growth decrease for Δpket2 in turbulent AC-auto, and (3) flux via PKET pathway reaching up to 252% of the flux via phosphoglycerate mutase under AC-auto. All results imply that PKET pathway plays a crucial role under AC-auto by mitigating the decarboxylation occurring in OPP pathway and conversion of pyruvate to acetyl CoA linked to EMP glycolysis under the carbon scarce environment. Finally, our model predicted that PKETs have low affinity to S7P as a substrate.
Slr0967 and Sll0939 induced by the SphR response regulator in Synechocystis sp. PCC 6803 are essential for growth under acid stress conditions
