title: Metabolic profile of 1,5-diaminopentane producing Corynebacterium glutamicum under scale-down conditions: Blueprint for robustness to bioreactor inhomogeneities.
abstract: Performance losses during scale-up are described since decades, but are still one of the major obstacles for industrial bioprocess development. Consequently, robustness to inhomogeneous cultivation environments is an important quality of industrial production organisms. Especially, Corynebacterium glutamicum was proven to have an outstanding resistance against rapid changes of oxygen and substrate availability as occurring in industrial scale bioreactors. This study focuses on the identification of metabolic key mechanisms for this robustness to get a deeper insight and provide future targets for process orientated strain development. A 1,5-diaminopentane producing C. glutamicum strain was cultivated in a two compartment scale-down device to create short-term environmental changes simulating industrial scale cultivation conditions. Using multi omics based methods, it is shown, that central metabolism is flexibly rearranged under short-term oxygen depletion and carbon source excess to overcome shortage in NAD+recycling. In order to balance the redox state, key enzymes for the non-oxygen dependent fermentative NAD+regeneration were significantly up-regulated while parts of non-essential pathways were down-regulated. The transfer of the cells back into the well aerated zones with low substrate concentration triggers an additional upregulation of genes for the re-assimilation of previously formed side products, showing L-lactate forming and utilizing reactions being active at the same time. Especially L-lactate as reversible and flexible external buffer for carbon and redox equivalents puts C. glutamicum in a robust position to deal with inhomogeneity in large scale processes. Biotechnol. Bioeng. 2017;114: 560-575. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Forschungszentrum Jülich GmbH, Institute of Bio- and Geosciences, IBG-1: Biotechnology, Wilhelm-Johnen-Straße, 52425 Jülich, Germany.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Limberg
authors.affiliation: Forschungszentrum Jülich GmbH, Institute of Bio- and Geosciences, IBG-1: Biotechnology, Wilhelm-Johnen-Straße, 52425 Jülich, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Schulte
authors.affiliation: Forschungszentrum Jülich GmbH, Institute of Bio- and Geosciences, IBG-1: Biotechnology, Wilhelm-Johnen-Straße, 52425 Jülich, Germany.
authors.forename: Tita
authors.initials: T
authors.lastname: Aryani
authors.affiliation: Forschungszentrum Jülich GmbH, Institute of Bio- and Geosciences, IBG-1: Biotechnology, Wilhelm-Johnen-Straße, 52425 Jülich, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Mahr
authors.affiliation: Forschungszentrum Jülich GmbH, Institute of Bio- and Geosciences, IBG-1: Biotechnology, Wilhelm-Johnen-Straße, 52425 Jülich, Germany.
authors.forename: Meike
authors.initials: M
authors.lastname: Baumgart
authors.affiliation: Forschungszentrum Jülich GmbH, Institute of Bio- and Geosciences, IBG-1: Biotechnology, Wilhelm-Johnen-Straße, 52425 Jülich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bott
authors.affiliation: Forschungszentrum Jülich GmbH, Institute of Bio- and Geosciences, IBG-1: Biotechnology, Wilhelm-Johnen-Straße, 52425 Jülich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wiechert
authors.affiliation: Forschungszentrum Jülich GmbH, Institute of Bio- and Geosciences, IBG-1: Biotechnology, Wilhelm-Johnen-Straße, 52425 Jülich, Germany.|Institute of Biotechnology, RWTH Aachen University, Aachen, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Oldiges
mesh_terms: D019149:Bioreactors / Q000382:microbiology*; D048230:Corynebacterium glutamicum / Q000378:metabolism*; D003959:Diamines / Q000032:analysis / Q000378:metabolism*; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D010100:Oxygen / Q000032:analysis / Q000378:metabolism; D010420:Pentanes / Q000032:analysis / Q000378:metabolism*
chemical_list: D003959:Diamines; D010420:Pentanes; C033353:pentane; D005947:Glucose; D010100:Oxygen
keywords: 1,5-diaminopentane; Corynebacterium glutamicum; bioreactor inhomogeneities; oxygen deprivation; scale-down; scale-up