Background Information on GBL system
Bacterial communication and Synthetic Biology
Many microorganisms produce antibiotics in order to gain a competitive advantage over other organisms for their survival. However, coordination between members of the population is critical as the end products can be fatal for the colony if produced in an unregulated manner. One prominent mechanism employed is a mechanism of "voting" by members of the colony, by sensing and producing signalling molecules. If a large number of surrounding neigbours are producing the signalling molecules in response to an environmental cue, this is likely to indicate the right moment to produce antibiotics. [1]
These mechanisms have been targeted by synthetic biology whose core aim is the design and engineering of complex biological systems with functionalities that do not exist in nature. In order to accomplish this, novel regulatory circuits need to be developed, which will enable the precise control of gene expression over a wide range of conditions. [2] The bacterium Vibrio fischeri has been in the spotlight in recent years, due to its communication mechanism known as "quorum sensing" (QS). [3] This organism produces acyl homoserine lactone (AHL) as a signal molecule and exports it to the environment. As the colony grows and the cell density increases, the concentration of AHL in the environment also rises, until it reaches a threshold which activates the expression of specific genes responsible for the emission of light.
The system responsible for the production of AHL is composed of two genes and their encoding regulatory proteins LuxI and LuxR. LuxI is the actual synthase of the autoinducer and LuxR, is a repressor belonging to the TetR family. [4] AHL forms a complex with the LuxR protein and together they bind to a short sequence called lux box which both enhances the transcription of LuxI (thus leading to even further accumulation of AHL) and activates the bioluminescence gene cluster. This positive feedback loop leads to a behaviour similar to a bistable switch, with the system being either in the "on" or in the "off" state, and with a zone of unstable intermediate states between them.
Regulation in Streptomyces coelicolor
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.
- ↑ M. Biarnes-Carrera, R. Breitling, E. Takano Butyrolactone signalling circuits for synthetic biology. Current Opinion in Chemical Biology 28: 91-98, 2015.
- ↑ Z. Li and S. K. Nair, Quorum sensing: how bacteria can coordinate activity and synchronize their response to external signals? Protein Science 21(10): 1403-1417, 2012.
- ↑ Ramos JL, Martínez-Bueno M, Molina-Henares AJ, et al. , The TetR Family of Transcriptional Repressors Microbiol Mol Biol Rev., 69(2): 326–356, 2005.
