In large-scale fed-batch production processes, microbes are exposed to heterogeneous substrate availability caused by long mixing times. Escherichia coli, the most common industrial host for recombinant protein production, reacts by recurring accumulation of the alarmone ppGpp and energetically wasteful transcriptional strategies. Here, we compare the regulatory responses of the stringent response mutant strain E. coli SR and its parent strain E. coli MG1655 to repeated nutrient starvation in a two-compartment scale-down reactor. Our data show that E. coli SR can withstand these stress conditions without a ppGpp-mediated stress response maintaining fully functional ammonium uptake and biomass formation. Furthermore, E. coli SR exhibited a substantially reduced short-term transcriptional response compared to E. coli MG1655 (less than half as many differentially expressed genes). E. coli SR proceeded adaptation via more general SOS response pathways by initiating negative regulation of transcription, translation and cell division. Our results show that locally induced stress responses propagating through the bioreactor do not result in cyclical induction and repression of genes in E. coli SR, but in a reduced and coordinated response, which makes it potentially suitable for large-scale production processes.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085953PMC
http://dx.doi.org/10.1111/1751-7915.13738DOI Listing

Publication Analysis

Top Keywords

stringent response
8
response mutant
8
mutant strain
8
production processes
8
coli
8
strain coli
8
coli mg1655
8
genes coli
8
response
6
transcriptional profiling
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!