The dynamic architecture of the metabolic switch in Streptomyces coelicolor.
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.
Nieselt
Kay
K
Center for Bioinformatics Tübingen, Department of Information and Cognitive Sciences, University of Tübingen, D-72076 Tübingen, Germany. nieselt@informatik.uni-tuebingen.de
Battke
Florian
F
Herbig
Alexander
A
Bruheim
Per
P
Wentzel
Alexander
A
Jakobsen
Øyvind M
ØM
Sletta
Håvard
H
Alam
Mohammad T
MT
Merlo
Maria E
ME
Moore
Jonathan
J
Omara
Walid A M
WA
Morrissey
Edward R
ER
Juarez-Hermosillo
Miguel A
MA
Rodríguez-García
Antonio
A
Nentwich
Merle
M
Thomas
Louise
L
Iqbal
Mudassar
M
Legaie
Roxane
R
Gaze
William H
WH
Challis
Gregory L
GL
Jansen
Ritsert C
RC
Dijkhuizen
Lubbert
L
Rand
David A
DA
Wild
David L
DL
Bonin
Michael
M
Reuther
Jens
J
Wohlleben
Wolfgang
W
Smith
Margaret C M
MC
Burroughs
Nigel J
NJ
Martín
Juan F
JF
Hodgson
David A
DA
Takano
Eriko
E
Breitling
Rainer
R
Ellingsen
Trond E
TE
Wellington
Elizabeth M H
EM
D000900:Anti-Bacterial Agents / Q000096:biosynthesis; D016000:Cluster Analysis; D005285:Fermentation; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D005810:Multigene Family; D012329:RNA, Bacterial / Q000235:genetics; D048372:Streptomyces coelicolor / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D012329:RNA, Bacterial