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Characterization and modeling of transcriptional cross-regulation in Acinetobacter baylyi ADP1

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  • Dayi Zhang
  • Yun Zhao
  • Yi He
  • Yun Wang
  • Yiyu Zhao
  • Yi Zheng
  • Xia Wei
  • Litong Zhang
  • Yuzhen Li
  • Tao Jin
  • Lin Wu
  • Hui Wang
  • Paul A. Davison
  • Junguang Xu
  • Wei E. Huang
<mark>Journal publication date</mark>07/2012
<mark>Journal</mark>ACS Synthetic Biology
Issue number7
Number of pages10
Pages (from-to)274-283
Publication StatusPublished
<mark>Original language</mark>English


Synthetic biology involves reprogramming and engineering of regulatory genes in innovative ways for the implementation of novel tasks. Transcriptional gene regulation systems induced by small molecules in prokaryotes provide a rich source for logic gates. Cross-regulation, whereby a promoter is activated by different molecules or different promoters are activated by one molecule, can be used to design an OR-gate and achieve cross-talk between gene networks in cells. Acinetobacter baylyi ADP1 is naturally transformable, readily editing its chromosomal DNA, which makes it a convenient chassis for synthetic biology. The catabolic genes for salicylate, benzoate, and catechol metabolism are located within a supraoperonic cluster (-sal-are-ben-cat-) in the chromosome of A. baylyi ADP 1, which are separately regulated by LysR-type transcriptional regulators (LTTRs). ADP1-based biosensors were constructed in which salA, benA, and catB were fused with a reporter gene cassette luxCDABE under the separate control of SalR, BenM, and CatM regulators. Salicylate, benzoate, catechol, and associated metabolites were found to mediate cross-regulation among sal, ben, and cat operons. A new mathematical model was developed by considering regulator-inducer binding and promoter activation as two separate steps. This model fits the experimental data well and is shown to predict cross-regulation performance.