The diatom species Pseudo-nitzschia australis can produce domoic acid (DA), a neurotoxin- responsible for amnesic shellfish poisoning. Copper (Cu) and zinc (Zn) are essential trace metals for marine phytoplankton, but they can become either limiting or toxic at pico- to subnanomolar ionic concentrations—levels that are can be reached in coastal ecosystems. The effect of exposure to these metals on DA production remains unclear for Cu and is largely unknown for Zn. In this study, we investigated the effects of toxic picomolar concentrations of Cu²⁺ and four non-limiting concentrations of Zn²⁺ on the metabolism and physiology of a toxic P. australis strain isolated from the coastal waters of North Biscay (France). Using principal component analysis, we observed changes in cell populations over time depending on metal exposure. Cu²⁺ toxicity was marked by a 35% decrease in maximum cell density and a reduction in growth rate (µ₊Cu = 0.55 µₐₓ). DA production was differentially modulated by the two metals: toxic Cu²⁺ levels stimulated DA synthesis (+200%), while elevated Zn²⁺ bioavailability significantly decreased it (by up to –85%), including when Zn²⁺ was combined with toxic levels of Cu²⁺ (–65%). We further discuss DA production by P. australis as a potential protective mechanism against oxidative stress. Additional data on intracellular glutathione (GSH) quotas—an important reactive oxygen species (ROS) scavenger and Cu²⁺ chelator— are presented and linked to Zn2+ bioavailability. GSH cell quotas were significantly correlated with DA production (p < 0.05) further supporting existing links between metal exposition, oxydative stress and DA production. This study suggests that ambient concentrations of Cu²⁺ and Zn²⁺ are critical factors regulating DA production in coastal marine systems
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