Inducing Secondary Metabolite Production by the Endophytic Fungus Fusarium tricinctum through Coculture with Bacillus subtilis

Abstract

Coculturing the fungal endophyte Fusarium tricinctum with the bacterium Bacillus subtilis 168 trpC2 on solid rice medium resulted in an up to 78-fold increase in the accumulation in constitutively present secondary metabolites that included lateropyrone (5), cyclic depsipeptides of the enniatin type (6-8), and the lipopeptide fusaristatin A (9). In addition, four compounds (1-4) including (-)-citreoisocoumarin (2) as well as three new natural products (1, 3, and 4) were not present in discrete fungal and bacterial controls and only detected in the cocultures. The new compounds were identified as macrocarpon C (1), 2-(carboxymethylamino)benzoic acid (3), and (-)-citreoisocoumarinol (4) by analysis of the 1D and 2D NMR and HRMS data. Enniatins B1 (7) and A1 (8), whose production was particularly enhanced, inhibited the growth of the cocultivated B. subtilis strain with minimal inhibitory concentrations (MICs) of 16 and 8 μg/mL, respectively, and were also active against Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecalis with MIC values in the range 2-8 μg/mL. In addition, lateropyrone (5), which was constitutively present in F. tricinctum, displayed good antibacterial activity against B. subtilis, S. aureus, S. pneumoniae, and E. faecalis, with MIC values ranging from 2 to 8 μg/mL. All active compounds were equally effective against a multiresistant clinical isolate of S. aureus and a susceptible reference strain of the same species.

Antibiotic dialogues: induction of silent biosynthetic gene clusters by exogenous small molecules

“…In this case, no growth inhibition of the bacterial strain was reported. Further, Proksch and colleagues have reported a 1.5-to 78-fold overproduction of bioactive metabolites from the ascomycete Fusarium tricinctum when cocultured with Bacillus subtilis (Ola et al 2013). These studies led to identification of four cryptic metabolites, three of which are known to be produced by the fungus.…”

Endophytic Fungi: As a Pool of Secondary Metabolites.

“…Because microbes in nature live in commun ities, growth of various fungi in co -culture with other organisms has been tested. Co-culture can indeed result in activation of silent gene clusters or in strongly increased expression (Ola et al 2013;Wu et al 2015b). Little-studied groups of fungi are considered to be potential sources of novel natural products for medicine and agriculture ).…”

Endophytic Fungi as a Source of Novel Metabolites

“…No antibacterial activity [123] (3S,4aR,7S)-7,8-dihydroxy-3-methyl-3,4,10,5,6,7-hexahydro-1H-isochromen- Pestaloficiol Q (49)…”