title: 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.
authors.affiliation: Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität Düsseldorf , Universitätsstrasse 1, Geb. 26.23, 40225 Düsseldorf, Germany.
authors.forename: Antonius R B
authors.initials: AR
authors.lastname: Ola
authors.forename: Dhana
authors.initials: D
authors.lastname: Thomy
authors.forename: Daowan
authors.initials: D
authors.lastname: Lai
authors.forename: Heike
authors.initials: H
authors.lastname: Brötz-Oesterhelt
authors.forename: Peter
authors.initials: P
authors.lastname: Proksch
mesh_terms: D030022:Aristolochia / Q000382:microbiology; D001412:Bacillus subtilis / Q000378:metabolism*; D018920:Coculture Techniques; D047630:Depsipeptides / Q000378:metabolism; D013293:Enterococcus faecalis / Q000187:drug effects; D005670:Fusarium / Q000737:chemistry*; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013211:Staphylococcus aureus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects
chemical_list: D047630:Depsipeptides; C100264:enniatins