Unravelling the γ-butyrolactone network in Streptomyces coelicolor by computational ensemble modelling

by Areti Tsigkinopoulou, Eriko Takano, Rainer Breitling

Antibiotic production is coordinated in the Streptomyces coelicolor population through the use of diffusible signaling molecules of the γ-butyrolactone (GBL) family. The GBL regulatory system involves a small, and not completely defined two-gene network which governs a potentially bi-stable switch between the “on” and “off” states of antibiotic production. The use of this circuit as a tool for synthetic biology has been hampered by a lack of mechanistic understanding of its functionality. We hereby present the creation and analysis of a versatile and adaptable ensemble model of the Streptomyces GBL system (detailed information on all model mechanisms and parameters is documented in http://www.systemsbiology.ls.manchester.ac.uk/wiki/index.php/Main_Page). We use the model to explore a range of previously proposed mechanistic hypotheses, including transcriptional interference, antisense RNA interactions between the mRNAs of the two genes, and various alternative regulatory activities. Our results suggest that transcriptional interference alone is not sufficient to explain the system’s behavior. Instead, antisense RNA interactions seem to be the system’s driving force, combined with an aggressive scbR promoter. The computational model can be used to further challenge and refine our understanding of the system’s activity and guide future experimentation.

Paper source
Plos Journal

READ MORE  Early transmission of sensitive strain slows down emergence of drug resistance in Plasmodium vivax

Ominy science editory team

A team of dedicated users that search, fetch and publish research stories for Ominy science.

Copyright 2020 Ominy science

Content published here is for information purposes alone.