title: Intertwining nutrient-sensory networks and the control of antibiotic production in Streptomyces.
abstract: Actinobacteria are producers of a plethora of natural products of agricultural, biotechnological and clinical importance. In an era where mankind has to deal with rapidly spreading antimicrobial resistance, streptomycetes are of particular importance as producers of half of all antibiotics used in the clinic. Genome sequencing efforts revealed that their capacity as antibiotic producers has been underestimated, in particular as many biosynthetic pathways are silent under standard laboratory conditions. Here we review the global regulatory networks that control antibiotic production in streptomycetes, with emphasis on carbon- and aminosugar-related nutrient sensory pathways. Recent research has revealed intriguing connections between these regulons, and overlap and antagonism between the activities of among others the global regulatory proteins AtrA, DasR and Rok7B7 as well as GlnR (nitrogen control) and PhoP (phosphate control), are discussed. Finally, we provide ideas as to how these novel insights might help us to find ways to activate the transcription of silent biosynthetic gene clusters.
authors.affiliation: Molecular Biotechnology, Institute of Biology, Leiden University, Sylviusweg 72, Leiden, 2333BE, The Netherlands.
authors.forename: Mia
authors.initials: M
authors.lastname: Urem
authors.affiliation: Department of Ecophysiology, Max Planck Institute for Terrestrial Microbiology, Karl-von-Frisch-Strasse 10, Marburg, 35043, Germany.
authors.forename: Magdalena A
authors.initials: MA
authors.lastname: Świątek-Połatyńska
authors.affiliation: InBioS, Centre for Protein Engineering, University of Liège, Liège, B-4000, Belgium.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Rigali
authors.affiliation: Molecular Biotechnology, Institute of Biology, Leiden University, Sylviusweg 72, Leiden, 2333BE, The Netherlands. g.wezel@biology.leidenuniv.nl.|Department of Microbial Ecology, Netherlands Institute of Ecology (NIOO-KNAW), Droevendaalsesteeg 10, Wageningen, 6708 PB, The Netherlands. g.wezel@biology.leidenuniv.nl.
authors.forename: Gilles P
authors.initials: GP
authors.lastname: van Wezel
mesh_terms: D000606:Amino Sugars / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000378:metabolism; D053898:Biosynthetic Pathways; D002244:Carbon / Q000378:metabolism; D009584:Nitrogen / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D018085:Regulon / Q000235:genetics; D013302:Streptomyces / Q000378:metabolism*
chemical_list: D000606:Amino Sugars; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D010710:Phosphates; D002244:Carbon; D009584:Nitrogen