title: Automated design of bacterial genome sequences.
abstract: BACKGROUND
  Organisms have evolved ways of regulating transcription to better adapt to varying environments. Could the current functional genomics data and models support the possibility of engineering a genome with completely rearranged gene organization while the cell maintains its behavior under environmental challenges? How would we proceed to design a full nucleotide sequence for such genomes?
  
  
  RESULTS
  As a first step towards answering such questions, recent work showed that it is possible to design alternative transcriptomic models showing the same behavior under environmental variations than the wild-type model. A second step would require providing evidence that it is possible to provide a nucleotide sequence for a genome encoding such transcriptional model. We used computational design techniques to design a rewired global transcriptional regulation of Escherichia coli, yet showing a similar transcriptomic response than the wild-type. Afterwards, we "compiled" the transcriptional networks into nucleotide sequences to obtain the final genome sequence. Our computational evolution procedure ensures that we can maintain the genotype-phenotype mapping during the rewiring of the regulatory network. We found that it is theoretically possible to reorganize E. coli genome into 86% fewer regulated operons. Such refactored genomes are constituted by operons that contain sets of genes sharing around the 60% of their biological functions and, if evolved under highly variable environmental conditions, have regulatory networks, which turn out to respond more than 20% faster to multiple external perturbations.
  
  
  CONCLUSIONS
  This work provides the first algorithm for producing a genome sequence encoding a rewired transcriptional regulation with wild-type behavior under alternative environments.
authors.forename: Javier
authors.initials: J
authors.lastname: Carrera
authors.affiliation: School of Life Sciences, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK. Alfonso.Jaramillo@warwick.ac.uk.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Jaramillo
mesh_terms: D000465:Algorithms; D001331:Automation; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D053263:Gene Regulatory Networks / Q000235:genetics; D016680:Genome, Bacterial / Q000235:genetics*; D023281:Genomics / Q000379:methods*; D009876:Operon / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors