Welcome to the In-Silico Model of butyrolactone regulation in Streptomyces coelicolor
Contents
About the Project
Streptomyces coelicolor are Gram-positive soil-dwelling bacteria, which are known as prolific source of secondary metabolites, such as antibiotics. As the end-products can be toxic even to the producing organisms, antibiotic production is carefully coordinated in the bacterial population. This is achieved through the use of SCB1-3, the diffusible signalling molecules of the γ-butyrolactone (GBL) family, in a manner analogous to acyl homoserine lactone (AHL)-based quorum sensing (QS). The GBL regulatory system involves a small, yet complex two gene (ScbA and ScbR) network, which governs a bistable switch between the "on" and "off" states of antibiotic production. The mechanism of this network is not fully defined, although several alternative scenarios have been proposed. The aim of this project is therefore the design and analysis of a model which will successfully describe the GBL regulatory system and allow reliable predictions of its behaviour. The complete elucidation of this system could potentially lead to the design of robust and sensitive systems with significant applications as orthologous regulatory circuits in synthetic biology and biotechnology.
Description of the Model
Several alternative scenarios for the mechanism of action of the GBL system have been previously proposed. Our aim is to create a unified model which will include them all and enable their parallel or combined analysis. The scenarios investigated are the following:
- The formation of a complex between proteins ScbA and ScbR, which relieves the self-repression of ScbR and the repression of ScbA by ScbR, while at the same time activates the production of ScbA and in turn of SCB1. [1]
- The effect of transcriptional interference (collisions between the elongating RNAPs which leads to transcriptional termination) due to the overlap of the two genes' promoter regions by 53 bp and by the convergent transcription of the two genes. This results in a decrease in expression of full-length RNAs from both promoters and production of truncated RNAs. [2] [3]
- The antisense effect conferred by convergent transcription of the ScbR and ScbA genes. In this case, transcripts with a segment of complementary sequence may lead to interactions between sense-antisense full length transcripts of the two genes, thus leading to the formation of a fast degrading complex of the two mRNAs and inhibition of translation. [2]
A schematic description of the model is provided below. More information can be obtained by clicking on each reaction.
Reactions
The model consists of two compartments, the Cell and the Environment. The reactions of each compartment are listed below.
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Cell |
Cell-Environment Environment |
Parameter Overview
References
- ↑ S. Mehra, S. Charaniya, E. Takano, and W.-S. Hu. A bistable gene switch for antibiotic biosynthesis: The butyrolactone regulon in streptomyces coelicolor. PLoS ONE, 3(7), 2008.
- ↑ 2.0 2.1 A. Chatterjee, L. Drews, S. Mehra, E. Takano, Y.N. Kaznessis, and W.-S. Hu. Convergent transcription in the butyrolactone regulon in streptomyces coelicolor confers a bistable genetic switch for antibiotic biosynthesis. PLoS ONE, 6(7), 2011.
- ↑ E. Takano. γ-butyrolactones: Streptomyces signalling molecules regulating antibiotic production and differentiation. Current Opinion in Microbiology, 9(3):287–294, 2006.
