ИСТИНА

The oldest prokaryotic photoautotrophic organisms, cyanobacteria, produce a large number of different metabolites. Eutrophication of lakes and rivers leads to cyanobacterial blooms and production of many dangerous cyanotoxins [1]. Understanding the biological functions of cyanotoxins is an important scientific task. The object of our study is a water-soluble neurotoxic non-protein amino acid, beta-N-methylamino-L-alanine (BMAA). Its biological role in cyanobacterial metabolism is of fundamental scientific and practical interest. Earlier BMAA inhibitory effect on nitrogen fixation and on heterocyst differentiation was shown in a diazotrophic cyanobacterium Anabaena sp. PCC 7120 under conditions of nitrogen starvation. It was also found that the transcription of both heterocyst specific genes hetR and hepA is down regulated by BMAA in Anabaena sp. PCC 7120 during nitrogen deprivation [2]. Herein we present a comprehensive examination of the Anabaena sp. PCC 7120 proteome under BMAA treatment in nitrogen starvation growth conditions. A remarkable pleiotropic regulatory effect of BMAA on this cyanobacterium proteome was found. BMAA disturbs nitrogen and carbon metabolisms, which are tightly co-regulated in cyanobacteria cells. This cyanotoxin affects the key nitrogen regulatory protein PII and some of its protein partners, as well as influences several proteins, involved in heterocyst differentiation and functioning. Moreover, BMAA disturbs photosynthesis process, carbon fixation and carbon dioxide concentrating mechanism, amino acids metabolism, as well as changes the amount of proteins involved in cell-signaling and stress-defense. Thus BMAA suppresses all major metabolic pathways in the cyanobacterial cell, causing internal cellular stress. The existence of such stress is evidenced by activation of the cell protective mechanisms that lead to an increase in the amount of chaperone proteins, a number of proteases, several signal proteins, oxidative stress defense proteins and DNA repair enzymes. The main primary targets of the BMAA action are apparently metabolic processes involved 2-oxyglutarate, glutamate, regulatory protein PII. This is the first proteomic study of the effects of BMAA on diazotrophic cyanobacteria cells under nitrogen limited conditions that allows us to have a deeper look at the regulation of intracellular metabolism of Anabaena sp. PCC 7120.