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Review
. 2022 Aug 7;14(8):539.
doi: 10.3390/toxins14080539.

Non-Proteinogenic Amino Acid β-N-Methylamino-L-Alanine (BMAA): Bioactivity and Ecological Significance

Olga A Koksharova  1   2 , Nina A Safronova  1
Affiliations
Review

Non-Proteinogenic Amino Acid β-N-Methylamino-L-Alanine (BMAA): Bioactivity and Ecological Significance

Olga A Koksharova et al. Toxins (Basel). .

Abstract

Research interest in a non-protein amino acid β-N-methylamino-L-alanine (BMAA) arose due to the discovery of a connection between exposure to BMAA and the occurrence of neurodegenerative diseases. Previous reviews on this topic either considered BMAA as a risk factor for neurodegenerative diseases or focused on the problems of detecting BMAA in various environmental samples. Our review is devoted to a wide range of fundamental biological problems related to BMAA, including the molecular mechanisms of biological activity of BMAA and the complex relationships between producers of BMAA and the environment in various natural ecosystems. At the beginning, we briefly recall the most important facts about the producers of BMAA (cyanobacteria, microalgae, and bacteria), the pathways of BMAA biosynthesis, and reliable methods of identification of BMAA. The main distinctive feature of our review is a detailed examination of the molecular mechanisms underlying the toxicity of BMAA to living cells. A brand new aspect, not previously discussed in any reviews, is the effect of BMAA on cyanobacterial cells. These recent studies, conducted using transcriptomics and proteomics, revealed potent regulatory effects of BMAA on the basic metabolism and cell development of these ancient photoautotrophic prokaryotes. Exogenous BMAA strongly influences cell differentiation and primary metabolic processes in cyanobacteria, such as nitrogen fixation, photosynthesis, carbon fixation, and various biosynthetic processes involving 2-oxoglutarate and glutamate. Cyanobacteria were found to be more sensitive to exogenous BMAA under nitrogen-limited growth conditions. We suggest a hypothesis that this toxic diaminoacid can be used by phytoplankton organisms as a possible allelopathic tool for controlling the population of cyanobacterial cells during a period of intense competition for nitrogen and other resources in various ecosystems.

Keywords: LC-MS/MS; algae; cyanobacteria; diatoms; glutamate receptors; nitrogen metabolism; oxidative stress; photosynthesis; proteomics; toxic molecules.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
This diagram shows the bioaccumulation pathways of BMAA.
Figure 2
Figure 2
Antimicrobial peptides (galantin (a) and paenilamicins (b,c)), which include BMAA (modified figure from [14]).
Figure 3
Figure 3
The scheme shows the effects of BMAA on model species of animals and plants, as well as cyanobacteria and diatoms.
Figure 4
Figure 4
Illustration of the regulatory effect of BMAA on cell differentiation and nitrogenase activity in diazotrophic cyanobacteria under various growth conditions [109]. BMAA up-regulates protein PII in nitrogen-replete conditions [108] and down-regulates protein PII in conditions of nitrogen starvation [107]. In mature heterocysts BMAA strongly inhibits the expression of the nifH gene in diazotrophic-growth conditions [105].
Figure 5
Figure 5
The effect of BMAA on various proteins in the cells of cyanobacteria Nostoc sp. PCC 7120 in nitrogen-replete conditions (A) and under conditions of nitrogen starvation (B). The light-blue arrows represent interactions between regulatory proteins PII and NicA and their main protein partners [173]. The red arrows indicate the downregulation of proteins and processes (↓), and the blue arrows indicate the upregulation of proteins and processes (↑) (modified figure from [107,108]).
Figure 6
Figure 6
Illustration of the “allelopathic tool” hypothesis. BMAA can be used in the fight for organic nitrogen [109].
See this image and copyright information in PMC

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