Putative biosynthesis mechanism of the neurotoxin β-N-methylamino-L-alanine in marine diatoms based on a transcriptomics approach

The neurotoxin beta-N-methylamino-L-alanine (BMAA) has been presumed as an environmental cause of human neurodegenerative disorders, such as Alzheimer's disease. Marine diatoms Thalassiosira minima are demonstrated here to produce BMAA-containing proteins in axenic culture while the isomer diaminobutyric acid was bacte-rially produced. In the co-culture with Cyanobacterium aponinum, diatom growth was inhibited but the biosyn-thesis of BMAA-containing proteins was stimulated up to seven times higher than that of the control group by cell-cell interactions. The stimulation effect was not caused by the cyanobacterial filtrate. Nitrogen depriva-tion also doubled the BMAA content of T. minima cells. Transcriptome analysis of the diatom in mixed culture revealed that pathways involved in T. minima metabolism and cellular functions were mainly influenced, including KEGG pathways valine and leucine/isoleucine degradation, endocytosis, pantothenate and CoA biosynthesis, and SNARE interactions in vesicular transport. Based on the expression changes of genes related to protein biosynthesis, it was hypothesized that ubiquitination and autophagy suppression, and limited COPII vesicles transport accuracy and efficiency were responsible for biosynthesis of BMAA-containing proteins in T. minima. This study represents a first application of transcriptomics to investigate the biological processes associated with BMAA biosynthesis in diatoms.

Automated summary

This study demonstrates that marine diatoms Thalassiosira minima are capable of producing BMAA-containing proteins in axenic culture and in co-culture with Cyanobacterium aponinum. The biosynthesis of BMAA-containing proteins in diatoms is influenced by factors such as cell-cell interactions and nitrogen deprivation. Transcriptome analysis reveals the pathways and genes associated with diatom metabolism and cellular functions that are affected by BMAA biosynthesis.