title: Epigenome manipulation as a pathway to new natural product scaffolds and their congeners.
abstract: The covalent modification of chromatin is an important control mechanism used by fungi to modulate the transcription of genes involved in secondary metabolite production. To date, both molecular-based and chemical approaches targeting histone and DNA posttranslational processes have shown great potential for rationally directing the activation and/or suppression of natural-product-encoding gene clusters. In this Highlight, the organization of the fungal epigenome is summarized and strategies for manipulating chromatin-related targets are presented. Applications of these techniques are illustrated using several recently published accounts in which chemical-epigenetic methods and mutant studies were successfully employed for the de novo or enhanced production of structurally diverse fungal natural products (e.g., anthraquinones, cladochromes, lunalides, mycotoxins, and nygerones).
authors.affiliation: Natural Products Discovery Group and Graduate Program in Ecology and Evolutionary Biology, Department of Chemistry and Biochemistry, 620 Parrington Oval, Room 208, University of Oklahoma, Norman, OK 73019, USA. rhcichewicz@ou.edu
authors.forename: Robert H
authors.initials: RH
authors.lastname: Cichewicz
mesh_terms: D001688:Biological Products / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D005658:Fungi / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016678:Genome; D015394:Molecular Structure; D017386:Sequence Homology, Amino Acid; D013237:Stereoisomerism
chemical_list: D001688:Biological Products