Epigenome manipulation as a pathway to new natural product scaffolds and their congeners.
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).
Cichewicz
Robert H
RH
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
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
D001688:Biological Products