title: Butyrate influences intracellular levels of adenine and adenine derivatives in the fungus Penicillium restrictum.
abstract: Butyrate, a small fatty acid, has an important role in the colon of ruminants and mammalians including the inhibition of inflammation and the regulation of cell proliferation. There is also growing evidence that butyrate is influencing the histone structure in mammalian cells by inhibition of histone deacetylation. Butyrate shows furthermore an antimicrobial activity against fungi, yeast and bacteria, which is linked to its toxicity at a high concentration. In fungi there are indications that butyrate induces the production of secondary metabolites potentially via inhibition of histone deacetylases. However, information about the influence of butyrate on growth, primary metabolite production and metabolism, besides lipid catabolism, in fungi is scarce. We have identified the filamentous fungus Penicillium (P.) restrictum as a susceptible target for butyrate treatment in an antimicrobial activity screen. The antimicrobial activity was detected only in the mycelium of the butyrate treated culture. We investigated the effect of butyrate ranging from low (0.001mM) to high (30mM), potentially toxic, concentrations on biomass and antimicrobial activity. Butyrate at high concentrations (3 and 30mM) significantly reduced the fungal biomass. In contrast P. restrictum treated with 0.03mM of butyrate showed the highest antimicrobial activity. We isolated three antimicrobial active compounds, active against Staphylococcus aureus, from P. restrictum cellular extracts treated with butyrate: adenine, its derivate hypoxanthine and the nucleoside derivate adenosine. Production of all three compounds was increased at low butyrate concentrations. Furthermore we found that butyrate influences the intracellular level of the adenine nucleoside derivate cAMP, an important signalling molecule in fungi and various organisms. In conclusion butyrate treatment increases the intracellular levels of adenine and its respective derivatives.
authors.affiliation: Institute for Milk Hygiene, University of Veterinary Medicine Vienna, Vienna, Austria; Research Platform Bioactive Microbial Metabolites, Bioresources and Technologies Campus Tulln, Tulln, Donau, Austria. Electronic address: Christoph.zutz@vetmeduni.ac.at.
authors.forename: Christoph
authors.initials: C
authors.lastname: Zutz
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, USA; Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan, Taiwan. Electronic address: ymchiangster@gmail.com.
authors.forename: Yi Ming
authors.initials: YM
authors.lastname: Chiang
authors.affiliation: Institute of Animal Nutrition and Functional Plant Compounds, University of Veterinary Medicine Vienna, Vienna, Austria. Electronic address: bettinafaehnrich@gmx.at.
authors.forename: Bettina
authors.initials: B
authors.lastname: Faehnrich
authors.affiliation: Division of Chemistry of Renewables, Department of Chemistry, BOKU University of Natural Resources and Life Sciences, Tulln, Donau, Austria. Electronic address: markus.bacher@boku.ac.at.
authors.forename: Markus
authors.initials: M
authors.lastname: Bacher
authors.affiliation: Research Platform Bioactive Microbial Metabolites, Bioresources and Technologies Campus Tulln, Tulln, Donau, Austria; Center for Analytical Chemistry, Department for Agrobiotechnology (IFA-Tulln), BOKU University of Natural Resources and Life Sciences, Tulln/Donau, Austria. Electronic address: Roland.Hellinger@boku.ac.at.
authors.forename: Roland
authors.initials: R
authors.lastname: Hellinger
authors.affiliation: Research Platform Bioactive Microbial Metabolites, Bioresources and Technologies Campus Tulln, Tulln, Donau, Austria; Center for Analytical Chemistry, Department for Agrobiotechnology (IFA-Tulln), BOKU University of Natural Resources and Life Sciences, Tulln/Donau, Austria. Electronic address: Bernhard.kluger@boku.ac.at.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kluger
authors.affiliation: Institute for Milk Hygiene, University of Veterinary Medicine Vienna, Vienna, Austria. Electronic address: Martin.wagner@vetmeduni.ac.at.
authors.forename: Martin
authors.initials: M
authors.lastname: Wagner
authors.affiliation: Research Platform Bioactive Microbial Metabolites, Bioresources and Technologies Campus Tulln, Tulln, Donau, Austria; Fungal Genetics and Genomics Unit, Department of Applied Genetics and Cell Biology, BOKU University of Natural Resources and Life Sciences Vienna, Tulln/Donau, Austria. Electronic address: joseph.strauss@boku.ac.at.
authors.forename: Joseph
authors.initials: J
authors.lastname: Strauss
authors.affiliation: Institute for Milk Hygiene, University of Veterinary Medicine Vienna, Vienna, Austria. Electronic address: Kathrin.rychli@vetmeduni.ac.at.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Rychli
mesh_terms: D000225:Adenine / Q000096:biosynthesis / Q000378:metabolism*; D000241:Adenosine / Q000737:chemistry / Q000378:metabolism; D000890:Anti-Infective Agents / Q000494:pharmacology*; D018533:Biomass; D002087:Butyrates / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D000242:Cyclic AMP / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D019271:Hypoxanthine / Q000737:chemistry / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D010407:Penicillium / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D013172:Spores, Fungal / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D002087:Butyrates; D019271:Hypoxanthine; D000242:Cyclic AMP; D000225:Adenine; D000241:Adenosine
keywords: Penicillium restrictum; adenine; adenosine; butyrate; cAMP; hypoxanthine