title: Metabolites from the Fungal Endophyte Aspergillus austroafricanus in Axenic Culture and in Fungal-Bacterial Mixed Cultures.
abstract: The endophytic fungus Aspergillus austroafricanus isolated from leaves of the aquatic plant Eichhornia crassipes was fermented axenically on solid rice medium as well as in mixed cultures with Bacillus subtilis or with Streptomyces lividans. Chromatographic analysis of EtOAc extract of axenic cultures afforded two new metabolites, namely, the xanthone dimer austradixanthone (1) and the sesquiterpene (+)-austrosene (2), along with five known compounds (3-7). Austradixanthone (1) represents the first highly oxygenated heterodimeric xanthone derivative. When A. austroafricanus was grown in mixed cultures with B. subtilis or with S. lividans, several diphenyl ethers (8-11) including the new austramide (8) were induced up to 29-fold. The structures of new compounds were unambiguously elucidated using 1D- and 2D-NMR spectroscopy, HRESIMS, and chemical derivatization. Compound 7 exhibited weak cytotoxicity against the murine lymphoma L5178Y cell line (EC50 is 12.6 μM). In addition, compounds 9 and 10, which were enhanced in mixed fungal/bacterial cultures, proved to be active against Staphylococcus aureus (ATCC 700699) with minimal inhibitory concentrations (MICs) of 25 μM each (6.6 μg/mL), whereas compound 11 revealed moderate antibacterial activity against B. subtilis 168 trpC2 with an MIC value of 34.8 μM (8 μg/mL).
authors.affiliation: Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität Düsseldorf , Universitätsstrasse 1, Geb. 26.23, 40225 Düsseldorf, Germany.|Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University , 35516 Mansoura, Egypt.
authors.forename: Weaam
authors.initials: W
authors.lastname: Ebrahim
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University , 35516 Mansoura, Egypt.
authors.forename: Mona
authors.initials: M
authors.lastname: El-Neketi
authors.affiliation: Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität Düsseldorf , Universitätsstrasse 1, Geb. 26.23, 40225 Düsseldorf, Germany.
authors.forename: Laura-Isabell
authors.initials: LI
authors.lastname: Lewald
authors.affiliation: Pharmacognosy Department, Faculty of Pharmacy, King Saud University , Riyadh, Saudi Arabia.
authors.forename: Raha S
authors.initials: RS
authors.lastname: Orfali
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Health Science Center , 100191 Beijing, People's Republic of China.
authors.forename: Wenhan
authors.initials: W
authors.lastname: Lin
authors.affiliation: Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität Düsseldorf , Universitätsstrasse 1, Geb. 26.23, 40225 Düsseldorf, Germany.
authors.forename: Nidja
authors.initials: N
authors.lastname: Rehberg
authors.affiliation: Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität Düsseldorf , Universitätsstrasse 1, Geb. 26.23, 40225 Düsseldorf, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Kalscheuer
authors.affiliation: Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität Düsseldorf , Universitätsstrasse 1, Geb. 26.23, 40225 Düsseldorf, Germany.
authors.forename: Georgios
authors.initials: G
authors.lastname: Daletos
authors.affiliation: Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität Düsseldorf , Universitätsstrasse 1, Geb. 26.23, 40225 Düsseldorf, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Proksch
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry; D001230:Aspergillus / Q000737:chemistry*; D001412:Bacillus subtilis / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification*; D013211:Staphylococcus aureus / Q000187:drug effects; D044004:Xanthones / Q000737:chemistry / Q000302:isolation & purification*
chemical_list: D000900:Anti-Bacterial Agents; D012717:Sesquiterpenes; D044004:Xanthones; C000610480:austradixanthone; C000610481:austrosene