Evaluating the outcomes of submerged co-cultivation: production of lovastatin and other secondary metabolites by Aspergillus terreus in fungal co-cultures

Abstract

The goal of the study was to compare the production of secondary metabolites by Aspergillus terreus ATCC 20542 under the conditions of submerged mono- and co-cultivation. The suggested experimental scheme encompassed a diverse set of co-culture initiation strategies differing mostly with respect to the development stage of tested fungal strains at the moment of their confrontation. Three species of filamentous fungi exhibiting distinct patterns of morphological evolution under submerged conditions, namely Penicillium rubens, Chaetomium globosum, and Mucor racemosus, were selected as the co-cultivation partners of A. terreus. The choice of the co-cultivated species and the approach of co-culture triggering noticeably influenced the levels of lovastatin (mevinolinic acid), (+)-geodin, asterric acid, and butyrolactone I in the broth. Even though the evaluated co-cultures did not lead to the increased titers of lovastatin relative to standard monocultures, the biosynthesis of the remaining three metabolites was either enhanced or inhibited depending on the experimental variant. The production of butyrolactone I turned out to be particularly affected by the presence of C. globosum. Interestingly, in the A. terreus/C. globosum co-cultures, the decrease of lovastatin concentration was recorded. According to the most probable scenario, lovastatin was in this case converted to monacolin J acid, a polyketide molecule that may be applied as a substrate for the synthesis of statin drugs. The study revealed that the spores of two distinct fungal species, namely A. terreus and C. globosum, co-agglomerate under submerged conditions to form pellets. Finally, the biosynthetic performance of co-cultures involving four fungal species was evaluated.