Systems, methods, and compositions for modifying the metabolsim of plants and of eucaryotic microbes, and for culturing them for the production of lipids with high concentrations of omega-3 highly unsaturated fatty acids (HUFA) suitable for human and animal consumption as food additives or for use in pharmaceutical and industrial products. The metabolic modifier is added to a fermentation or growth medium, and is selected from the group consisting essentially of a fatty acid metabolism inhibitor, glycolysis inhibitor, a bifunctional compound that links a fatty acid metabolism inhibitor to a glycolysis inhibitor, glucose, insulin, and a plant growth factor.