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.
Highlights
Fungal secondary metabolites constitute a rich group of bioactive molecules, some of which are considered to be promising leads in drug development projects (Adrio and Demain 2003; Brakhage 2013; Demain 2014; Keller et al 2005).Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.While it has been 90 years since an antibiotic penicillin was serendipitously discovered as a metabolic product of a mold Penicillium rubens (Fleming 1929; Houbraken et al 2011), the scientific and industrial interest in fungal secondary metabolism remains unabated
The outcomes of submerged co-cultivation of A. terreus with P. rubens, C. globosum, and M. racemosus were evaluated according to six experimental schemes depicted as BExperiments 1–6^ in Fig. 1 and the results are presented below
The decrease of lovastatin concentration observed in the current study, in the case of the A. terreus/C. globosum co-cultures, was probably due to the enzymatic hydrolysis leading to monacolin J acid
Summary
While it has been 90 years since an antibiotic penicillin was serendipitously discovered as a metabolic product of a mold Penicillium rubens (originally referred to as Penicillium notatum) (Fleming 1929; Houbraken et al 2011), the scientific and industrial interest in fungal secondary metabolism remains unabated. The strategies aimed at elucidating the complex machinery of biosynthetic pathways and inducing the formation of previously unknown chemical structures are becoming more and more sophisticated. A diverse set of experimental approaches aimed at deciphering the biochemical potential of filamentous
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