Neurotoxin β-N-methylamino-L-alanine (BMAA) as an environmental factor possibly triggers human neurodegenerative diseases such as amyotrophic lateral sclerosis/ parkinsonism dementia complex (ALS/PDC), and Alzheimer’s disease. Our research disclosed that marine diatoms could produce BMAA-containing proteins and BMAA could be transferred and accumulated along food chains. The biosynthesis of BMAA in diatoms could be stimulated by the co-culture with cyanobacterium or iron (Fe) limitation conditions. Transcriptome sequencing and subcellular distribution location of these proteins in Thalassiosira minima demonstrated that protein processing in endoplasmic reticulum, where SNARE interactions in vesicular transport and proteasome pathways mainly benefited their accumulation. Based on the mutated diatom strain and biochemical experiments via addition of the recombinant cysteine synthase (cysK) and methylamine, the cysK enzyme was disclosed to catalyze the cysteine residues in peptide chains to in situ form BMAA structure in diatom cells. Our study first disclosed the biosynthesis mechanism of neurotoxin BMAA in marine diatoms, which provides a clue to further explore its biological significance and the pathological mechanism for human neurodegenerative diseases. 

β-N-methylamino-L-alanine (BMAA), neurodegenerative diseases, diatom, iron-limitation, biosynthesis