Putative Biosynthesis Mechanism of the Neurotoxin Β-N-Methylamino-L-Alanine in Marine Diatoms Based on a Transcriptomics Approach

Abstract

The neurotoxin β - 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 here demonstrated to produce BMAA-containing proteins in axenic culture while the isomer diaminobutyric acid was bacterially produced. In the co-culture with Cyanobacterium aponinum , diatom growth was inhibited but the biosynthesis of BMAA-containing proteins was stimulated. This stimulation was caused by cell-cell interactions but not by the cyanobacterial filtrate. Nitrogen deprivation 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.

Keywords: Diatom, β-N-methylamino-L-alanine (BMAA), biosynthesis, ubiquitination, autophagy