Genomic mining of prokaryotic repressors for orthogonal logic gates

Nat Chem Biol. 2014 Feb;10(2):99-105. doi: 10.1038/nchembio.1411. Epub 2013 Dec 8.

Abstract

Genetic circuits perform computational operations based on interactions between freely diffusing molecules within a cell. When transcription factors are combined to build a circuit, unintended interactions can disrupt its function. Here, we apply 'part mining' to build a library of 73 TetR-family repressors gleaned from prokaryotic genomes. The operators of a subset were determined using an in vitro method, and this information was used to build synthetic promoters. The promoters and repressors were screened for cross-reactions. Of these, 16 were identified that both strongly repress their cognate promoter (5- to 207-fold) and exhibit minimal interactions with other promoters. Each repressor-promoter pair was converted to a NOT gate and characterized. Used as a set of 16 NOT/NOR gates, there are >10(54) circuits that could be built by changing the pattern of input and output promoters. This represents a large set of compatible gates that can be used to construct user-defined circuits.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Base Sequence
  • Gene Regulatory Networks / genetics
  • Genome, Bacterial / genetics
  • Genomics*
  • Operator Regions, Genetic
  • Prokaryotic Cells*
  • Promoter Regions, Genetic / genetics
  • Repressor Proteins / genetics*
  • Small Molecule Libraries*

Substances

  • Repressor Proteins
  • Small Molecule Libraries