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

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.

β-N-Methylamino-L-Alanine (BMAA) Modulates the Sympathetic Regulation and Homeostasis of Polyamines

“…BMAA could damage sympathetic regulation by inducing oxidative stress in adrenergic nerve endings, such as neurotoxin 6-hydroxydopamine [ 42 ], and by inhibiting the loading of secretory vesicles similarly to reserpine [ 44 ]. On the other hand, BMAA is not only accumulated and stored in muscle tissues, as observed in fishes and animals (chicken) feed with blue mussels-based feed [ 45 , 46 ], but it also suppresses the muscle regulation of adrenaline.…”

How Single Site Mutations Can Help Understanding Structure Formation of Amyloid β1−40

“…The nonproteinogenic amino acid β ‐methylamino‐ l ‐alanine (BMAA) is produced by a wide range of bacteria, e.g., cyanobacteria, which possibly reaches humans via the food chain. [ 126 ] BMAA is a neurotoxin and potentially correlated with a few neurological diseases, such as amyotrophic lateral sclerosis, Parkinson's disease, and also Alzheimer's disease upon incorporation into relevant proteins. [ 127 ] This is, however, a controversial field of research as varying results regarding their relationship are obtained.…”

Metabolome Profiling of Marrubium peregrinum L. and Marrubium friwaldskyanum Boiss Reveals Their Potential as Sources of Plant-Based Pharmaceuticals

“…In general, a large part of the biologically active substances derived from amino acid precursors and some non-proteinogenic amino acids such as homoserine and ornithine, found in abundance in Marrubium flowers, might serve as intermediates for the synthesis of small bioactive peptides [27,28]. L-phenylalanine is one of the key amino acids in relation to the phenolic secondary metabolites synthesized via shikimate biosynthesis and its accumulation in flowers is not causal.…”