The MtrAB two-component system controls antibiotic production in Streptomyces coelicolor A3(2)

Nicolle F. Som; Daniel  Heine; Neil Holmes; Felicity Knowles; Govind Chandra; Ryan F. Seipke; Paul A. Hoskisson; Barrie Wilkinson; Matthew I. Hutchings

doi:10.1099/mic.0.000524

The MtrAB two-component system controls antibiotic production in Streptomyces coelicolor A3(2)

Nicolle F. Som, Daniel Heine, Neil Holmes, Felicity Knowles, Govind Chandra, Ryan F. Seipke, Paul A. Hoskisson, Barrie Wilkinson, Matthew I. Hutchings

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Abstract

MtrAB is a highly conserved two component system implicated in the regulation of cell division in the Actinobacteria. It coordinates DNA replication with cell division in the unicellular Mycobacterium tuberculosis and links antibiotic production to sporulation in the filamentous Streptomyces venezuelae. Chloramphenicol biosynthesis is directly regulated by MtrA in S. venezuelae and deletion of mtrB constitutively activates MtrA and results in constitutive over-production of chloramphenicol. Here we report that in Streptomyces coelicolor, MtrA binds to sites upstream of developmental genes and the genes encoding ActII-1, ActII-4 and RedZ, which are cluster situated regulators of the antibiotics actinorhodin (Act) and undecylprodigiosin (Red). Consistent with this, deletion of mtrB switches on production of Act, Red and streptorubin B, a product of the Red pathway. Thus, we propose that MtrA is a key regulator that links antibiotic production to development and it can be used to upregulate antibiotic production in distantly related streptomycetes.

Original language	English
Pages (from-to)	1415-1419
Number of pages	5
Journal	Microbiology
Volume	163
Issue number	10
Early online date	8 Sep 2017
DOIs	https://doi.org/10.1099/mic.0.000524
Publication status	Published - Oct 2017

Keywords

sporulation
Streptomyces
cryptic gene clusters
antibiotics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1099/mic.0.000524Licence: CC BY

Published manuscript
This is an open access article published by the Microbiology Society under the Creative Commons Attribution License
Final published version, 774 KBLicence: CC BY

Partner choice predictions: How does a host control its microbiome?
Hutchings, M., Murrell, C., Yu, D., Al-Bassam, M. & Patrick, E.
Natural Environment Research Council
1/07/15 → 30/06/18
Project: Research
Isolation and characterisation of novel antimycotics
Hutchings, M. & Yu, D.
Medical Research Council
1/08/09 → 31/07/12
Project: Research

Cite this

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title = "The MtrAB two-component system controls antibiotic production in Streptomyces coelicolor A3(2)",

abstract = "MtrAB is a highly conserved two component system implicated in the regulation of cell division in the Actinobacteria. It coordinates DNA replication with cell division in the unicellular Mycobacterium tuberculosis and links antibiotic production to sporulation in the filamentous Streptomyces venezuelae. Chloramphenicol biosynthesis is directly regulated by MtrA in S. venezuelae and deletion of mtrB constitutively activates MtrA and results in constitutive over-production of chloramphenicol. Here we report that in Streptomyces coelicolor, MtrA binds to sites upstream of developmental genes and the genes encoding ActII-1, ActII-4 and RedZ, which are cluster situated regulators of the antibiotics actinorhodin (Act) and undecylprodigiosin (Red). Consistent with this, deletion of mtrB switches on production of Act, Red and streptorubin B, a product of the Red pathway. Thus, we propose that MtrA is a key regulator that links antibiotic production to development and it can be used to upregulate antibiotic production in distantly related streptomycetes.",

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AU - Som, Nicolle F.

AU - Heine, Daniel

AU - Holmes, Neil

AU - Knowles, Felicity

AU - Chandra, Govind

AU - Seipke, Ryan F.

AU - Hoskisson, Paul A.

AU - Wilkinson, Barrie

AU - Hutchings, Matthew I.

PY - 2017/10

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N2 - MtrAB is a highly conserved two component system implicated in the regulation of cell division in the Actinobacteria. It coordinates DNA replication with cell division in the unicellular Mycobacterium tuberculosis and links antibiotic production to sporulation in the filamentous Streptomyces venezuelae. Chloramphenicol biosynthesis is directly regulated by MtrA in S. venezuelae and deletion of mtrB constitutively activates MtrA and results in constitutive over-production of chloramphenicol. Here we report that in Streptomyces coelicolor, MtrA binds to sites upstream of developmental genes and the genes encoding ActII-1, ActII-4 and RedZ, which are cluster situated regulators of the antibiotics actinorhodin (Act) and undecylprodigiosin (Red). Consistent with this, deletion of mtrB switches on production of Act, Red and streptorubin B, a product of the Red pathway. Thus, we propose that MtrA is a key regulator that links antibiotic production to development and it can be used to upregulate antibiotic production in distantly related streptomycetes.

AB - MtrAB is a highly conserved two component system implicated in the regulation of cell division in the Actinobacteria. It coordinates DNA replication with cell division in the unicellular Mycobacterium tuberculosis and links antibiotic production to sporulation in the filamentous Streptomyces venezuelae. Chloramphenicol biosynthesis is directly regulated by MtrA in S. venezuelae and deletion of mtrB constitutively activates MtrA and results in constitutive over-production of chloramphenicol. Here we report that in Streptomyces coelicolor, MtrA binds to sites upstream of developmental genes and the genes encoding ActII-1, ActII-4 and RedZ, which are cluster situated regulators of the antibiotics actinorhodin (Act) and undecylprodigiosin (Red). Consistent with this, deletion of mtrB switches on production of Act, Red and streptorubin B, a product of the Red pathway. Thus, we propose that MtrA is a key regulator that links antibiotic production to development and it can be used to upregulate antibiotic production in distantly related streptomycetes.

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KW - Streptomyces

KW - cryptic gene clusters

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DO - 10.1099/mic.0.000524

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JF - Microbiology

SN - 1350-0872

IS - 10

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The MtrAB two-component system controls antibiotic production in Streptomyces coelicolor A3(2)

Abstract

Keywords

UN SDGs

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Projects

Partner choice predictions: How does a host control its microbiome?

Isolation and characterisation of novel antimycotics

Cite this