title: Advanced continuous cultivation methods for systems microbiology.
abstract: Increasing the throughput of systems biology-based experimental characterization of in silico-designed strains has great potential for accelerating the development of cell factories. For this, analysis of metabolism in the steady state is essential as only this enables the unequivocal definition of the physiological state of cells, which is needed for the complete description and in silico reconstruction of their phenotypes. In this review, we show that for a systems microbiology approach, high-resolution characterization of metabolism in the steady state--growth space analysis (GSA)--can be achieved by using advanced continuous cultivation methods termed changestats. In changestats, an environmental parameter is continuously changed at a constant rate within one experiment whilst maintaining cells in the physiological steady state similar to chemostats. This increases the resolution and throughput of GSA compared with chemostats, and, moreover, enables following of the dynamics of metabolism and detection of metabolic switch-points and optimal growth conditions. We also describe the concept, challenge and necessary criteria of the systematic analysis of steady-state metabolism. Finally, we propose that such systematic characterization of the steady-state growth space of cells using changestats has value not only for fundamental studies of metabolism, but also for systems biology-based metabolic engineering of cell factories.
authors.affiliation: Tallinn University of Technology, Department of Food Processing, Ehitajate tee 5, 19086 Tallinn, Estonia.|Competence Center of Food and Fermentation Technologies, Akadeemia tee 15a, 12618 Tallinn, Estonia.
authors.forename: Kaarel
authors.initials: K
authors.lastname: Adamberg
authors.affiliation: Competence Center of Food and Fermentation Technologies, Akadeemia tee 15a, 12618 Tallinn, Estonia.
authors.forename: Kaspar
authors.initials: K
authors.lastname: Valgepea
authors.affiliation: Competence Center of Food and Fermentation Technologies, Akadeemia tee 15a, 12618 Tallinn, Estonia.|Tallinn University of Technology, Department of Chemistry, Akadeemia tee 15, 12618 Tallinn, Estonia.
authors.forename: Raivo
authors.initials: R
authors.lastname: Vilu
mesh_terms: D006801:Humans; D008828:Microbiological Techniques / Q000379:methods / Q000639:trends; D008829:Microbiology; D049490:Systems Biology / Q000379:methods / Q000639:trends