%0 Journal Article %1 ISI:000404123100019 %A Simen, Joana Danica %A Loeffler, Michael %A Jaeger, Guenter %A Schaeferhoff, Karin %A Freund, Andreas %A Matthes, Jakob %A Mueller, Jan %A Takors, Ralf %A RecogNice-Team, %C 111 RIVER ST, HOBOKEN 07030-5774, NJ USA %D 2017 %I WILEY %J MICROBIAL BIOTECHNOLOGY %K myown %N 4, SI %P 858-872 %R 10.1111/1751-7915.12713 %T Transcriptional response of Escherichia coli to ammonia and glucose fluctuations %U https://doi.org/10.1111/1751-7915.12713 %V 10 %X In large-scale production processes, metabolic control is typically achieved by limited supply of essential nutrients such as glucose or ammonia. With increasing bioreactor dimensions, microbial producers such as Escherichia coli are exposed to changing substrate availabilities due to limited mixing. In turn, cells sense and respond to these dynamic conditions leading to frequent activation of their regulatory programmes. Previously, we characterized short- and long-term strategies of cells to adapt to glucose fluctuations. Here, we focused on fluctuating ammonia supply while studying a continuously running two-compartment bioreactor system comprising a stirred tank reactor (STR) and a plug-flow reactor (PFR). The alarmone ppGpp rapidly accumulated in PFR, initiating considerable transcriptional responses after 70s. About 400 genes were repeatedly switched on/off when E.coli returned to the STR. E.coli revealed highly diverging long-term transcriptional responses in ammonia compared to glucose fluctuations. In contrast, the induction of stringent regulation was a common feature of both short-term responses. Cellular ATP demands for coping with fluctuating ammonia supply were found to increase maintenance by 15\%. The identification of genes contributing to the increased ATP demand together with the elucidation of regulatory mechanisms may help to create robust cells and processes for large-scale application.

@article{ISI:000404123100019, abstract = {{In large-scale production processes, metabolic control is typically achieved by limited supply of essential nutrients such as glucose or ammonia. With increasing bioreactor dimensions, microbial producers such as Escherichia coli are exposed to changing substrate availabilities due to limited mixing. In turn, cells sense and respond to these dynamic conditions leading to frequent activation of their regulatory programmes. Previously, we characterized short- and long-term strategies of cells to adapt to glucose fluctuations. Here, we focused on fluctuating ammonia supply while studying a continuously running two-compartment bioreactor system comprising a stirred tank reactor (STR) and a plug-flow reactor (PFR). The alarmone ppGpp rapidly accumulated in PFR, initiating considerable transcriptional responses after 70s. About 400 genes were repeatedly switched on/off when E.coli returned to the STR. E.coli revealed highly diverging long-term transcriptional responses in ammonia compared to glucose fluctuations. In contrast, the induction of stringent regulation was a common feature of both short-term responses. Cellular ATP demands for coping with fluctuating ammonia supply were found to increase maintenance by 15\%. The identification of genes contributing to the increased ATP demand together with the elucidation of regulatory mechanisms may help to create robust cells and processes for large-scale application.}}, added-at = {2018-06-08T11:31:29.000+0200}, address = {{111 RIVER ST, HOBOKEN 07030-5774, NJ USA}}, affiliation = {{Takors, R (Reprint Author), Univ Stuttgart, Inst Biochem Engn, Allmandring 31, D-70569 Stuttgart, Germany. Simen, Joana Danica; Loeffler, Michael; Freund, Andreas; Mueller, Jan; Takors, Ralf, Univ Stuttgart, Inst Biochem Engn, Allmandring 31, D-70569 Stuttgart, Germany. Jaeger, Guenter; Schaeferhoff, Karin; Matthes, Jakob, Univ Tubingen, Inst Med Genet \& Appl Genom, Calwerstr 7, D-72076 Tubingen, Germany.}}, author = {Simen, Joana Danica and Loeffler, Michael and Jaeger, Guenter and Schaeferhoff, Karin and Freund, Andreas and Matthes, Jakob and Mueller, Jan and Takors, Ralf and RecogNice-Team}, author-email = {{takors@ibvt.uni-stuttgart.de}}, biburl = {https://puma.ub.uni-stuttgart.de/bibtex/20095858374df5d681b0eb9cdebd7e22e/ralftakors}, da = {{2018-01-26}}, doc-delivery-number = {{EY6VZ}}, doi = {{10.1111/1751-7915.12713}}, funding-acknowledgement = {{Bundesministerium fur Bildung und Forschung {[}FKZ0316178A]}}, funding-text = {{Bundesministerium fur Bildung und Forschung (FKZ0316178A).}}, interhash = {2e4c9778b7cc07f1ccbea984855f0c7b}, intrahash = {0095858374df5d681b0eb9cdebd7e22e}, issn = {{1751-7915}}, journal = {{MICROBIAL BIOTECHNOLOGY}}, journal-iso = {{Microb. Biotechnol.}}, keywords = {myown}, keywords-plus = {{IN-VIVO ANALYSIS; SCALE-DOWN; GENE-EXPRESSION; STRINGENT RESPONSE; CORYNEBACTERIUM-GLUTAMICUM; DIFFERENTIAL EXPRESSION; FERMENTATION PROCESSES; NITROGEN LIMITATION; STARVATION; BIOREACTOR}}, language = {{English}}, month = {{JUL}}, number = {{4, SI}}, number-of-cited-references = {{62}}, oa = {{gold}}, pages = {{858-872}}, publisher = {{WILEY}}, research-areas = {{Biotechnology \& Applied Microbiology; Microbiology}}, times-cited = {{4}}, timestamp = {2018-06-08T09:31:29.000+0200}, title = {{Transcriptional response of Escherichia coli to ammonia and glucose fluctuations}}, type = {{Article}}, unique-id = {{ISI:000404123100019}}, url = {https://doi.org/10.1111/1751-7915.12713}, usage-count-last-180-days = {{3}}, usage-count-since-2013 = {{3}}, volume = {{10}}, web-of-science-categories = {{Biotechnology \& Applied Microbiology; Microbiology}}, year = {{2017}} }