Induced secondary metabolites from the endophytic fungus Aspergillus versicolor through bacterial co-culture and OSMAC approaches

Abstract

Two new cryptic 3,4-dihydronaphthalen-(2H)-1-one (1-tetralone) derivatives, aspvanicin A(1) and its epimer aspvanicin B (2), as well as several known cryptic metabolites (3-8), were obtained from the ethyl acetate extract of the co-culture of the endophytic fungus Aspergillus versicolor KU258497 with the bacterium Bacillus subtilis 168 trpC2 on solid rice medium.When A. versicolor was cultured axenically in liquid Wickerham medium supplemented with 3.5% DMSO, an additional three known secondary metabolites (9-11) were isolated that were lacking when the fungus was fermented on rice medium. The structures of the new compounds were elucidated using one-and two-dimensional NMR spectroscopy as well as HRESIMS. The relative and absolute configurations of 1 and 2 were determined by the combination of NMR and electronic circular dichroism (ECD) analysis aided by DFT conformational analysis and TDDFT-ECD calculations. The ECD calculations revealed that although the sign of the blueshifted overlapping n-π* ECD transition follows the helicity rule of cyclic aryl ketones, the calculation of low-energy conformers and ECD spectra was necessary to determine the stereochemistry. All metabolites were assessed for their antibacterial and cytotoxic activities; one of the new diastereomers, compound 2, showed moderate cytotoxic activity against the mouse lymphoma cell line L5178Y.

Mapping the Fungal Battlefield: Using in situ Chemistry and Deletion Mutants to Monitor Interspecific Chemical Interactions Between Fungi

“…The problem of uneven topology can be overcome by using the droplet–liquid microjunction–surface sampling probe (droplet probe) (Kertesz and Van Berkel, 2010, 2013). Importantly, mapping the chemical entities of fungi as they compete in situ can address chemical ecology questions, such as where (spatially) and when (temporally) the compounds are biosynthesized, and such data are typically lost in previous studies on co-culturing fungi through the use of a traditional chemical extraction processes (Wakefield et al, 2017; Abdelwahab et al, 2018; Mandelare et al, 2018).…”

Induction of Cryptic Antifungal Pulicatin Derivatives from Pantoea Agglomerans by Microbial Co-Culture

“…The antimicrobial activity of the total extract, pure compounds (1)(2)(3)(4)(5)(6)(7)(8), including the positive controls, was evaluated by determining the minimum inhibitory concentrations (MIC). The broth microdilution method in sterile 96 well plates (Thermo Scientific Ltd., Loughborough, UK) was performed following the CLSI guidelines [14] and EUCAST guidelines [15] with slight modifications.…”

“…Our group has demonstrated the efficiency of the co-culture approach when investigating the hyper-arid desert bacterial isolate Streptomyces bullii which led to the induction of diverse fungal metabolites that were not traced in the axenic culture [7]. Induction of the cryptic metabolites aspvanicin A and its epimer aspvanicin B was reported from endophytic fungus Aspergillus versicolor KU258497 through its co-culture with the bacterium Bacillus subtilis 168 trpC2 [8]. Four new naphthoquinone dimers, fusatricinones A-D, and a new lateropyrone derivative, dihydrolateropyrone, were induced in the co-cultivation of the endophytic fungus Fusarium tricinctum with Streptomyces lividans [9].…”

Biosorption Potential of the Aspergillus sp. and Insights into Secondary Metabolism in the Presence of Copper and Lead

“…The study of possible modifications in the metabolism of this microorganism on a culture medium is a contribution to the one strainmany compounds (OSMAC) approach, which aims at the production of new substances through the awakening of silenced genes. [16][17][18][19][20]…”