title: Chemical perturbation of secondary metabolism demonstrates important links to primary metabolism.
abstract: Bacterially produced secondary metabolites are used as antibiotics, anticancer drugs, and for many other medicinal applications. The mechanisms that limit the production of these molecules in the laboratory are not well understood, and this has impeded the discovery of many important compounds. We have identified small molecules that remodel the yields of secondary metabolites in many actinomycetes and show that one set of these molecules does so by inhibiting fatty acid biosynthesis. This demonstrates a particularly intimate relationship between this primary metabolic pathway and secondary metabolism and suggests an approach to enhance the yields of metabolites for discovery and biochemical characterization.
authors.affiliation: Michael Degroote Institute for Infectious Disease Research, McMaster University, 1280 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Arryn
authors.initials: A
authors.lastname: Craney
authors.forename: Cory
authors.initials: C
authors.lastname: Ozimok
authors.forename: Sheila Marie
authors.initials: SM
authors.lastname: Pimentel-Elardo
authors.forename: Alfredo
authors.initials: A
authors.lastname: Capretta
authors.forename: Justin R
authors.initials: JR
authors.lastname: Nodwell
mesh_terms: D039903:Actinobacteria / Q000378:metabolism*; D000880:Anthraquinones / Q000737:chemistry / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005227:Fatty Acids / Q000096:biosynthesis*; D013058:Mass Spectrometry; D011353:Prodigiosin / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism; D013053:Spectrophotometry; D048372:Streptomyces coelicolor / Q000378:metabolism; D000095622:Benzoisochromanequinones
chemical_list: D000880:Anthraquinones; D000900:Anti-Bacterial Agents; D005227:Fatty Acids; D011353:Prodigiosin; D054852:Small Molecule Libraries; C010307:prodiginine; C013390:actinorhodin; D000095622:Benzoisochromanequinones