Intertwining nutrient-sensory networks and the control of antibiotic production in Streptomyces

TY - JOUR

T1 - Intertwining nutrient-sensory networks and the control of antibiotic production in Streptomyces

AU - Urem, Mia

AU - Świątek-Połatyńska, Magdalena A

AU - Rigali, Sébastien

AU - van Wezel, Gilles P

N1 - © 2016 John Wiley & Sons Ltd.

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - international

U2 - 10.1111/mmi.13464

DO - 10.1111/mmi.13464

M3 - Article

C2 - 27425419

SN - 0950-382X

VL - 102

SP - 183

EP - 195

JO - Molecular Microbiology

JF - Molecular Microbiology

IS - 2

ER -