Multiomics Study of Bacterial Growth Arrest in a Synthetic Biology Application

ACS Synth Biol. 2021 Nov 19;10(11):2910-2926. doi: 10.1021/acssynbio.1c00115. Epub 2021 Nov 5.


We investigated the scalability of a previously developed growth switch based on external control of RNA polymerase expression. Our results indicate that, in liter-scale bioreactors operating in fed-batch mode, growth-arrested Escherichia coli cells are able to convert glucose to glycerol at an increased yield. A multiomics quantification of the physiology of the cells shows that, apart from acetate production, few metabolic side effects occur. However, a number of specific responses to growth slow-down and growth arrest are launched at the transcriptional level. These notably include the downregulation of genes involved in growth-associated processes, such as amino acid and nucleotide metabolism and translation. Interestingly, the transcriptional responses are buffered at the proteome level, probably due to the strong decrease of the total mRNA concentration after the diminution of transcriptional activity and the absence of growth dilution of proteins. Growth arrest thus reduces the opportunities for dynamically adjusting the proteome composition, which poses constraints on the design of biotechnological production processes but may also avoid the initiation of deleterious stress responses.

Keywords: Escherichia coli; bioinformatics; growth switch; metabolic engineering; multiomics data integration; synthetic circuit.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / metabolism
  • Bioreactors / microbiology
  • DNA-Directed RNA Polymerases / genetics
  • DNA-Directed RNA Polymerases / metabolism
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism
  • Escherichia coli / physiology*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Gene Expression Regulation, Bacterial / genetics
  • Glucose / genetics
  • Glucose / metabolism
  • Glycerol / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Synthetic Biology / methods


  • Acetates
  • Escherichia coli Proteins
  • RNA, Messenger
  • DNA-Directed RNA Polymerases
  • Glucose
  • Glycerol