Malonylome Analysis Reveals the Involvement of Lysine Malonylation in Metabolism and Photosynthesis in Cyanobacteria

As
a recently validated reversible post translational modification,
lysine malonylation regulates diverse cellular processes from bacteria
to mammals, but its existence and function in photosynthetic organisms
remain unknown. Cyanobacteria are the most ancient group of photosynthetic
prokaryotes and contribute about 50% of the total primary production
on Earth. Previously, we reported the lysine acetylome in the model
cyanobacterium Synechocystis sp. PCC 6803 (Synechocystis). Here we performed the first proteomic survey
of lysine malonylation in Synechocystis using highly
accurate tandem mass spectrometry in combination with affinity purification.
We identified 598 lysine malonylation sites on 339 proteins with high
confidence in total. A bioinformatic analysis suggested that these
malonylated proteins may play various functions and were distributed
in diverse subcellular compartments. Among them, many malonylated
proteins were involved in cellular metabolism. The functional significance
of lysine malonylation in the metabolic enzyme activity of phosphoglycerate
kinase (PGK) was determined by site-specific mutagenesis and biochemical
studies. Interestingly, 27 proteins involved in photosynthesis were
found to be malonylated for the first time, suggesting that lysine
malonylation may be involved in photosynthesis. Thus our results provide
the first lysine malonylome in a photosynthetic organism and suggest
a previously unexplored role of lysine malonylation in the regulation
of metabolic processes and photosynthesis in Synechocystis as well as in other photosynthetic organisms.