Induction of Secondary Metabolites from the Marine-Derived Fungus Aspergillus versicolor through Co-cultivation with Bacillus subtilis

Abstract

A new cyclic pentapeptide, cotteslosin C (1), a new aflaquinolone, 22-epi-aflaquinolone B (3), and two new anthraquinones (9 and 10), along with thirty known compounds (2, 4 – 8, 11 – 34) were isolated from a co-culture of the sponge-associated fungus Aspergillus versicolor with Bacillus subtilis. The new metabolites were only detected in the co-culture extract, but not when the fungus was grown under axenic conditions. Furthermore, the co-culture extract exhibited an enhanced accumulation of the known constituents versicolorin B (14), averufin (16), and sterigmatocyctin (19) by factors of 1.5, 2.0, and 4.7, respectively, compared to the axenic fungal culture. The structures of the isolated compounds were elucidated on the basis of 1D and 2D NMR spectra and mass spectrometry as well as by comparison with literature data. The absolute configuration of compounds 3, 9, and 10 was determined by ECD (electronic circular dichroism) analysis aided by TDDFT-ECD (time-dependent density functional theory electronic circular dichroism) calculations. Compounds 15, 18 – 21, and 26 exhibited strong to moderate cytotoxic activity against the mouse lymphoma cell line L5178Y, with IC50 values ranging from 2.0 to 21.2 µM, while compounds 14, 16, 31, 32, and 33 displayed moderate inhibitory activities against several gram-positive bacteria, with MIC values ranging from 12.5 to 50 µM.

The Structural Diversity of Marine Microbial Secondary Metabolites Based on Co-Culture Strategy: 2009–2019

“…99 displayed weak cytotoxicity against another three human cancer cell lines, prostate DU145, melanoma MM418c5 and breast T47D, with EC 50 values of 90, 66 and 94 µg/mL, respectively [61]. (Figure 16) [38]. Both of them did not show significant cytotoxic activity towards mouse lymphoma cell line L5178Y, or even antibacterial activity against five Gram-positive microbes, including one S. aureus, two E. faecalis and two E. faecium [38].…”

“…Furthermore, non-significant results were obtained against lung (A549), prostate (PC3) and breast (MCF-7) human cancer cells compared with the positive control, etoposide [53]. (Figure 13) were isolated and identified from the mixed fermentation broth of the marine fungus A. versicolor and B. subtilis [38]. (Figure 13) were isolated and identified from the mixed fermentation broth of the marine fungus A. versicolor and B. subtilis [38].…”

“…(Figure 13) were isolated and identified from the mixed fermentation broth of the marine fungus A. versicolor and B. subtilis [38]. (Figure 13) were isolated and identified from the mixed fermentation broth of the marine fungus A. versicolor and B. subtilis [38]. (Figure 14), was purified and identified from a co-culture of two marine invertebrate-associated bacteria Micromonospora sp.…”

“…BM-05 and BM-05ML isolated from a brown algal species collected off Helgoland, North Sea, Germany, yielded a new cyclotripeptide, psychrophilin E (97) ( Figure 15) [30]. (Figure 16) [38]. Both of them did not show significant cytotoxic activity towards mouse lymphoma cell line L5178Y, or even antibacterial activity against five Gram-positive microbes, including one S. aureus, two E. faecalis and two E. faecium [38].…”

Furoic acid derivatives from the endophytic fungus Coniothyrium sp.

“…There are an estimated 1.5 million fungal species on Earth, of which only about 70 000 are currently described . Some endophytic fungal genera such as Aspergillus and Penicillium are well investigated, and their metabolic patterns are well known, even though new compounds are still reported . In this study, the endophytic fungus Coniothyrium sp.…”