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Metabolic profile of 1,5‐diaminopentane producing Corynebacterium glutamicum under scale‐down conditions: Blueprint for robustness to bioreactor inhomogeneities
Author(s) -
Limberg Michael H.,
Schulte Julia,
Aryani Tita,
Mahr Regina,
Baumgart Meike,
Bott Michael,
Wiechert Wolfgang,
Oldiges Marco
Publication year - 2017
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.26184
Subject(s) - corynebacterium glutamicum , bioreactor , bioprocess , robustness (evolution) , biochemical engineering , biology , biological system , chemistry , biochemistry , botany , engineering , paleontology , gene
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.