Production of the Neurotoxin BMAA by Marine Diatoms Drives Its Widespread Occurrence in Estuarine and Coastal Ecosystems

Phytoplankton are the primary producers of marine neurotoxins such
as β-N-methylamino-l-alanine (BMAA),
which cause seafood poisoning outbreaks in estuarine and coastal regions.
BMAA has gained much attention for its pathogenic link to Alzheimer’s
and Parkinson’s disease. However, whether BMAA accumulates
in diatoms under fluctuations in estuarine and coastal areas remains
largely unknown. In this study, we investigated BMAA biosynthesis
in the model diatom Phaeodactylum tricornutum under simulated conditions of fluctuating nitrogen and salinity
in estuarine regions. BMAA was detectable in P. tricornutum under all simulated seawater or hyper-eutrophic conditions, although
nitrogen source and salinity interactively impact BMAA accumulation.
In addition, high-nitrogen wastewater conditions promoted carbon metabolism,
including the Calvin cycle, glycolysis, fatty acid biosynthesis, and
decreased nitrogen metabolism and BMAA production. Finally, we proposed
and elucidated a complete biosynthetic pathway of BMAA originating
from glutamate, incorporating catalysis by S-adenosylmethionine
(SAM)-dependent methyltransferases in diatoms, as inferred through
artificial intelligence-based pathway analysis. This study marks the
first attempt to decipher the BMAA metabolic pathway in diatoms, which
provides a paradigm shift to identify conditions that trigger toxin
production and also provides valuable metrics to address the complexity
and unpredictability of monitoring and forecasting algal blooms.