Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.184 (LasR)
 897 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Burkholderia cenocepacia is an opportunistic human pathogen that encodes two LuxI-type acylhomoserine lactone (AHL) synthases and three LuxR-type AHL receptors. Of these, cepI and cepR form a cognate synthase/receptor pair, as do cciI and cciR, while cepR2 lacks a genetically linked AHL synthase gene. Another group showed that a cepR2 mutant overexpressed a cluster of linked genes that appear to direct the production of a secondary metabolite. We found that these same genes were upregulated by octanoylhomoserine lactone (OHL), which is synthesized by CepI. These data suggest that several cepR2-linked promoters are repressed by CepR2 and that CepR2 is antagonized by OHL. Fusions of two divergent promoters to lacZ were used to confirm these hypotheses, and promoter resections and DNase I footprinting assays revealed a single CepR2 binding site between the two promoters. This binding site lies well upstream of both promoters, suggesting an unusual mode of repression. Adjacent to the cepR2 gene is a gene that we designate cepS, which encodes an AraC-type transcription factor. CepS is essential for expression of both promoters, regardless of the CepR2 status or OHL concentration. CepS therefore acts downstream of CepR2, and CepR2 appears to function as a CepS antiactivator.
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PMID:A LuxR-type repressor of Burkholderia cenocepacia inhibits transcription via antiactivation and is inactivated by its cognate acylhomoserine lactone. 2313 52

One challenge for synthetic biologists is the predictable tuning of genetic circuit regulatory components to elicit desired outputs. Gene expression driven by ligand-inducible transcription factor systems must exhibit the correct ON and OFF characteristics: appropriate activation and leakiness in the presence and absence of inducer, respectively. However, the dynamic range of a promoter (i.e., absolute difference between ON and OFF states) is difficult to control. We report a method that tunes the dynamic range of ligand-inducible promoters to achieve desired ON and OFF characteristics. We build combinatorial sets of AraC-and LasR-regulated promoters containing -10 and -35 sites from synthetic and Escherichia coli promoters. Four sequence combinations with diverse dynamic ranges were chosen to build multi-input transcriptional logic gates regulated by two and three ligand-inducible transcription factors (LacI, TetR, AraC, XylS, RhlR, LasR, and LuxR). This work enables predictable control over the dynamic range of regulatory components.
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PMID:Tuning the dynamic range of bacterial promoters regulated by ligand-inducible transcription factors. 2930 24