Dataset Information

The dynamic architecture of the metabolic switch in Streptomyces coelicolor.

ABSTRACT: 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.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.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.

SUBMITTER: Nieselt K

PROVIDER: S-EPMC2824715 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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The dynamic architecture of the metabolic switch in Streptomyces coelicolor.

Nieselt Kay K 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

BMC genomics 20100106

<h4>Background</h4>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.<h4>Results</h4>Surprisingly, we find that the metabolic switch actually consists of multiple finely orchestrated switching events. Strongly cohere ...[more]

PMID: 20053288

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Project description:Many microorganisms, including bacteria of the class Streptomycetes, produce various secondary metabolites including antibiotics to gain a competitive advantage in their natural habitat. The production of these compounds is highly coordinated in a population to expedite accumulation to an effective concentration. Furthermore, as antibiotics are often toxic even to their producers, a coordinated production allows microbes to first arm themselves with a defense mechanism to resist their own antibiotics before production commences. One possible mechanism of coordination among individuals is through the production of signaling molecules. The gamma-butyrolactone system in Streptomyces coelicolor is a model of such a signaling system for secondary metabolite production. The accumulation of these signaling molecules triggers antibiotic production in the population. A pair of repressor-amplifier proteins encoded by scbA and scbR mediates the production and action of one particular gamma-butyrolactone, SCB1. Based on the proposed interactions of scbA and scbR, a mathematical model was constructed and used to explore the ability of this system to act as a robust genetic switch. Stability analysis shows that the butyrolactone system exhibits bistability and, in response to a threshold SCB1 concentration, can switch from an OFF state to an ON state corresponding to the activation of genes in the cryptic type I polyketide synthase gene cluster, which are responsible for production of the hypothetical polyketide. The switching time is inversely related to the inducer concentration above the threshold, such that short pulses of low inducer concentration cannot switch on the system, suggesting its possible role in noise filtering. In contrast, secondary metabolite production can be triggered rapidly in a population of cells producing the butyrolactone signal due to the presence of an amplification loop in the system. S. coelicolor was perturbed experimentally by varying concentrations of SCB1, and the model simulations match the experimental data well. Deciphering the complexity of this butyrolactone switch will provide valuable insights into how robust and efficient systems can be designed using "simple" two-protein networks.

Dataset Information

The dynamic architecture of the metabolic switch in Streptomyces coelicolor.

Publications

The dynamic architecture of the metabolic switch in Streptomyces coelicolor.

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