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Fungi are an inexhaustible source of bioactive metabolites that can be driven to find medicines for chronic diseases, as Alzheimer’s disease. In the present work, five species of soil-originated fungi ( Aspergillus chevalieri ,  Clonostachys rogersoniana ,  Fusarium nygamai ,  Penicillium  sp., and  Talaromyces calidicanius ) were submitted to mutual biotic stress aiming at activating the expression of metabolites capable of inhibiting the enzyme acetylcholinesterase. HPLC profiles showed that the  in vitro  biotic stress triggered the biosynthesis of metabolite-mediated defense responses. Five compounds present in the complex co-culture matrix were identified by Paper Spray Mass Spectrometry (PS-MS). The approach enhanced the biosynthesis of acetylcholinesterase inhibitors (up to 99.6% inhibition) in comparison with the individual cultures. The mutual biotic stress between  T. calidicanius  and  A. Chevalieri  led to the biosynthesis of a pool of metabolites statistically as efficient as serine ( p  &lt; 0.05), the positive control used in the experiments (99.6 and 99.1% inhibition, respectively).

Biotic stress caused by in vitro co-inoculation enhances the expression of acetylcholinesterase inhibitors by fungi