Multiomics Study of Bacterial Growth Arrest in a Synthetic Biology Application

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.