title: Epigenetic Manipulation of a Filamentous Fungus by the Proteasome-Inhibitor Bortezomib Induces the Production of an Additional Secondary Metabolite.
abstract: The use of epigenetic modifiers, such as histone deacetylase inhibitors and DNA methyltransferase inhibitors, has been explored increasingly as a technique to induce the production of additional microbial secondary metabolites. The application of such molecules to microbial cultures has been shown to upregulate otherwise suppressed genes, and in several cases has led to the production of new molecular structures. In this study, the proteasome inhibitor bortezomib was used to induce the production of an additional metabolite from a filamentous fungus (Pleosporales). The induced metabolite was previously isolated from a plant, but the configuration was not assigned until now; in addition, an analogue was isolated from a degraded sample, yielding a new compound. Proteasome inhibitors have not previously been used in this application and offer an additional tool for microbial genome mining.
authors: Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, P.O. Box 26170, Greensboro, North Carolina 27402, United States.
authors: Karen M
authors: KM
authors: VanderMolen
authors: Mycosynthetix, Inc., 505 Meadowlands Drive, Suite 103, Hillsborough, North Carolina 27278, United States.
authors: Blaise A
authors: BA
authors: Darveaux
authors: Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois 60612, United States.
authors: Wei-Lun
authors: WL
authors: Chen
authors: Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois 60612, United States.
authors: Steven M
authors: SM
authors: Swanson
authors: Mycosynthetix, Inc., 505 Meadowlands Drive, Suite 103, Hillsborough, North Carolina 27278, United States.
authors: Cedric J
authors: CJ
authors: Pearce
authors: Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, P.O. Box 26170, Greensboro, North Carolina 27402, United States.
authors: Nicholas H
authors: NH
authors: Oberlies