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Open Access Highly Accessed Research article

The dynamic architecture of the metabolic switch in Streptomyces coelicolor

Kay Nieselt1*, Florian Battke1, Alexander Herbig1, Per Bruheim23, Alexander Wentzel23, Øyvind M Jakobsen3, Håvard Sletta3, Mohammad T Alam4, Maria E Merlo45, Jonathan Moore11, Walid AM Omara10, Edward R Morrissey11, Miguel A Juarez-Hermosillo11, Antonio Rodríguez-García7, Merle Nentwich8, Louise Thomas9, Mudassar Iqbal11, Roxane Legaie11, William H Gaze10, Gregory L Challis6, Ritsert C Jansen4, Lubbert Dijkhuizen5, David A Rand11, David L Wild11, Michael Bonin12, Jens Reuther8, Wolfgang Wohlleben8, Margaret CM Smith9, Nigel J Burroughs11, Juan F Martín7, David A Hodgson10, Eriko Takano5, Rainer Breitling4, Trond E Ellingsen3 and Elizabeth MH Wellington10*

Author Affiliations

1 Center for Bioinformatics Tübingen, Department of Information and Cognitive Sciences, University of Tübingen, Sand 14, D-72076 Tübingen, Germany

2 Department of Biotechnology, Norwegian University of Science and Technology (NTNU), Sem Sælandsvei 6-8, N-7491 Trondheim, Norway

3 Department of Biotechnology, SINTEF Materials and Chemistry, Sem Sælandsvei 2a, N-7465 Trondheim, Norway

4 Groningen Bioinformatics Centre, University of Groningen, Kerklaan 30, 9751 NN Haren, the Netherlands

5 Department of Microbial Physiology, University of Groningen, Kerklaan 30, 9751 NN Haren, the Netherlands

6 Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK

7 Instituto de Biotecnología de León, INBIOTEC, Parque Científico de León, Av. Real 1, 24006 León, Spain, and Área de Microbiología, Universidad de León, Spain

8 Department of Microbiology/Biotechnology, University of Tübingen, Auf der Morgenstelle 28, D-72076 Tübingen, Germany

9 School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK

10 Department of Biological Sciences, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK

11 Warwick Systems Biology Centre, University of Warwick, Coventry House, Coventry, CV4 7AL, UK

12 Microarray Facility Tübingen, Calwer Strasse 7, D-72076 Tübingen, Germany

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BMC Genomics 2010, 11:10  doi:10.1186/1471-2164-11-10

Published: 6 January 2010

Abstract

Background

During the lifetime of a fermenter culture, the soil bacterium S. coelicolor undergoes a major metabolic switch from exponential growth to antibiotic production. We have studied gene expression patterns during this switch, using a specifically designed Affymetrix genechip and a high-resolution time-series of fermenter-grown samples.

Results

Surprisingly, we find that the metabolic switch actually consists of multiple finely orchestrated switching events. Strongly coherent clusters of genes show drastic changes in gene expression already many hours before the classically defined transition phase where the switch from primary to secondary metabolism was expected. The main switch in gene expression takes only 2 hours, and changes in antibiotic biosynthesis genes are delayed relative to the metabolic rearrangements. Furthermore, global variation in morphogenesis genes indicates an involvement of cell differentiation pathways in the decision phase leading up to the commitment to antibiotic biosynthesis.

Conclusions

Our study provides the first detailed insights into the complex sequence of early regulatory events during and preceding the major metabolic switch in S. coelicolor, which will form the starting point for future attempts at engineering antibiotic production in a biotechnological setting.