Lomonosov Moscow State University, Belozersky Institute of Physical-Chemical Biology, Leninskie Gory, 1-40, 119992 Moscow, Russia.
Institute of Molecular Genetics, Russian Academy of Sciences, Kurchatov Square, 2, 123182 Moscow, Russia.
Toxins (Basel). 2020 May 9;12(5):310. doi: 10.3390/toxins12050310.
The oldest prokaryotic photoautotrophic organisms, cyanobacteria, produce many different metabolites. Among them is the water-soluble neurotoxic non-protein amino acid beta-N-methylamino-L-alanine (BMAA), whose biological functions in cyanobacterial metabolism are of fundamental scientific and practical interest. An early BMAA inhibitory effect on nitrogen fixation and heterocyst differentiation was shown in strains of diazotrophic cyanobacteria sp. PCC 7120, PCC 73102 (ATCC 29133), and sp. strain 8963 under conditions of nitrogen starvation. Herein, we present a comprehensive proteomic study of (also called ) sp. PCC 7120 in the heterocyst formation stage affecting by BMAA treatment under nitrogen starvation conditions. BMAA disturbs proteins involved in nitrogen and carbon metabolic pathways, which are tightly co-regulated in cyanobacteria cells. The presented evidence shows that exogenous BMAA affects a key nitrogen regulatory protein, PII (GlnB), and some of its protein partners, as well as glutamyl-tRNA synthetase gltX and other proteins that are involved in protein synthesis, heterocyst differentiation, and nitrogen metabolism. By taking into account the important regulatory role of PII, it becomes clear that BMAA has a severe negative impact on the carbon and nitrogen metabolism of starving sp. PCC 7120 cells. BMAA disturbs carbon fixation and the carbon dioxide concentrating mechanism, photosynthesis, and amino acid metabolism. Stress response proteins and DNA repair enzymes are upregulated in the presence of BMAA, clearly indicating severe intracellular stress. This is the first proteomic study of the effects of BMAA on diazotrophic starving cyanobacteria cells, allowing a deeper insight into the regulation of the intracellular metabolism of cyanobacteria by this non-protein amino acid.
最古老的原核光合生物蓝细菌产生许多不同的代谢物。其中包括水溶性神经毒性非蛋白氨基酸β-N-甲基氨基-L-丙氨酸（BMAA），其在蓝细菌代谢中的生物学功能具有重要的科学和实际意义。在固氮蓝藻 sp. PCC 7120、PCC 73102（ATCC 29133）和 sp. 菌株 8963 的条件下，早期的 BMAA 抑制氮固定和异形胞分化的作用得到了证明在氮饥饿条件下。在此，我们对氮饥饿条件下 BMAA 处理影响异形胞形成阶段的 （也称为 ） sp. PCC 7120 进行了全面的蛋白质组学研究。BMAA 扰乱了参与氮碳代谢途径的蛋白质，这些蛋白质在蓝藻细胞中紧密协同调控。提出的证据表明，外源性 BMAA 影响关键的氮调节蛋白 PII（GlnB）及其一些蛋白伴侣，以及谷氨酰-tRNA 合成酶 gltX 和其他参与蛋白质合成、异形胞分化和氮代谢的蛋白。考虑到 PII 的重要调节作用，很明显 BMAA 对饥饿的 sp. PCC 7120 细胞的碳氮代谢有严重的负面影响。BMAA 扰乱了碳固定和二氧化碳浓缩机制、光合作用和氨基酸代谢。在存在 BMAA 的情况下，应激反应蛋白和 DNA 修复酶上调，这清楚地表明细胞内存在严重的应激。这是首次对 BMAA 对固氮饥饿蓝藻细胞的影响进行蛋白质组学研究，使我们能够更深入地了解这种非蛋白氨基酸对蓝藻细胞内代谢的调节。
