Forcing the Issue: Aromatic Tuning Facilitates Stimulus-Independent Modulation of a Two-Component Signaling Circuit
Number of Authors: 3
2015 (English)In: ACS synthetic biology, ISSN 2161-5063, Vol. 4, no 4, 474-481 p.Article in journal (Refereed) Published
Two-component signaling circuits allow bacteria to detect and respond to external stimuli Unfortunately, the input stimulus remains unidentified for the majority of these circuits Therefore, development of a synthetic method for stimulus independent modulation of these circuits is highly desirable because particular physiological or developmental processes could be controlled for biotechnological purposes without the need to identify the stimulus itself Here, we demonstrate that aromatic tuning, i.e., repositioning the aromatic residues commonly found at the cytoplasmic end of the receptor (EnvZ) transmembrane domain, facilitates stimulus-independent modulation of signal output from the EnvZ/OmpR osmosensing circuit of Escherichia coli. We found that these osmosensing circuits retained the ability to respond appropriately to increased external osmolaiity, suggesting that the tuned receptors were not locked in a single conformation. We also noted that circuits containing aromatically tuned variants became more sensitive to changes in the receptor concentration than their wild type counterpart, suggesting a new way to study mechanisms underpinning receptor concentration dependent robustness. We believe that aromatic tuning has several advantages compared to previous methods aimed at stimulus independent modulation of receptors and that it will be generally applicable to a wide range of two component circuits.
Place, publisher, year, edition, pages
2015. Vol. 4, no 4, 474-481 p.
aromatic tuning, two-component circuit engineering, stimulus-independent modulation, concentration-dependent robustness
IdentifiersURN: urn:nbn:se:su:diva-117483DOI: 10.1021/sb500261tISI: 000353313600015PubMedID: 25162177OAI: oai:DiVA.org:su-117483DiVA: diva2:821389