The linkage between nutrient supply, intracellular enzyme abundances and bacterial growth: New evidences from the central carbon metabolism of Corynebacterium glutamicum

Noack, Stephan; Voges, Raphael; Gätgens, Jochem; Wiechert, Wolfgang

doi:10.1016/j.jbiotec.2017.06.407

Cited by 13 publications

(14 citation statements)

References 42 publications

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“…Typically, relevant performance indicators (PIs) are determined, including biomass and product titers ( c X , c P ), specific rates for biomass growth ( μ ), substrate consumption ( q S ), and product formation ( q P ) as well as specific yields relating substrate conversion and product formation to biomass growth ( Y X/S , Y P/X ). These PIs are usually obtained by fitting experimental data to single mathematical expressions or small process models, preferably in an automated way . By comparing such PIs with reference values or defined benchmark settings, new strain variants and/or cultivation conditions can be found (see Figure ).…”

Section: Microbioreactor (Mbr) Systemsmentioning

confidence: 99%

Microbioreactor Systems for Accelerated Bioprocess Development

Hemmerich

Noack

Wiechert

et al. 2018

Biotechnology Journal

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138

143

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In recent years, microbioreactor (MBR) systems have evolved towards versatile bioprocess engineering tools. They provide a unique solution to combine higher experimental throughput with extensive bioprocess monitoring and control, which is indispensable to develop economically and ecologically competitive bioproduction processes. MBR systems are based either on down-scaled stirred tank reactors or on advanced shaken microtiter plate cultivation devices. Importantly, MBR systems make use of optical measurements for non-invasive, online monitoring of important process variables like biomass concentration, dissolved oxygen, pH, and fluorescence. The application range of MBR systems can be further increased by integration into liquid handling robots, enabling automatization and, thus standardization, of various handling and operation procedures. Finally, the tight integration of quantitative strain phenotyping with bioprocess development under industrially relevant conditions greatly increases the probability of finding the right combination of producer strain and bioprocess control strategy. This review will discuss the current state of the art in the field of MBR systems and we can readily conclude that their importance for industrial biotechnology will further increase in the near future.

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Section: Microbioreactor (Mbr) Systemsmentioning

confidence: 99%

Microbioreactor Systems for Accelerated Bioprocess Development

Hemmerich

Noack

Wiechert

et al. 2018

Biotechnology Journal

Self Cite

138

143

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“…In addition, MTPs enable a higher throughput to perform replicate ALE experiments under identical conditions and thus provide access to important quantities for analyzing the evolutionary process, e.g., in terms of beneficial mutation rates and the occurrence of fixed or converged mutations . It is noteworthy that the typical 1 mL working volume of standard MTPs is also sufficient to carry out further in‐depth characterizations of evolved strains using available spectrophotometric assays and quantitative omics technologies …”

Section: The Benefit Of Automationmentioning

confidence: 99%

Evolutionary engineering of Corynebacterium glutamicum

Stella

Wiechert

Noack

et al. 2019

Biotechnology Journal

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A unique feature of biotechnology is that we can harness the power of evolution to improve process performance. Rational engineering of microbial strains has led to the establishment of a variety of successful bioprocesses, but it is hampered by the overwhelming complexity of biological systems. Evolutionary engineering represents a straightforward approach for fitness‐linked phenotypes (e.g., growth or stress tolerance) and is successfully applied to select for strains with improved properties for particular industrial applications. In recent years, synthetic evolution strategies have enabled selection for increased small molecule production by linking metabolic productivity to growth as a selectable trait. This review summarizes the evolutionary engineering strategies performed with the industrial platform organism Corynebacterium glutamicum. An increasing number of recent studies highlight the potential of adaptive laboratory evolution (ALE) to improve growth or stress resistance, implement the utilization of alternative carbon sources, or improve small molecule production. Advances in next‐generation sequencing and automation technologies will foster the application of ALE strategies to streamline microbial strains for bioproduction and enhance our understanding of biological systems.

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“…They identified growth rate dependent expression of ribosomal proteins and of F 0 F 1 subunits of ATP-synthase. Another study with a systems biology viewpoint was recently performed by Noack et al (2017) conducting chemostat cultivations to record the proteomic response of C. glutamicum WT ATCC 13032 within a broad range of growth rates (μ = 0.05–0.35 h –1 ). Under the tested glucose-limited growth conditions, Noack et al (2017) concluded that metabolic fluxes within C. glutamicum ’s central carbon metabolism are likely more affected by concentrations of local substrates and allosteric metabolite effectors than by the concentration of enzymes.…”

Section: Introductionmentioning

confidence: 99%

“…Another study with a systems biology viewpoint was recently performed by Noack et al (2017) conducting chemostat cultivations to record the proteomic response of C. glutamicum WT ATCC 13032 within a broad range of growth rates (μ = 0.05–0.35 h –1 ). Under the tested glucose-limited growth conditions, Noack et al (2017) concluded that metabolic fluxes within C. glutamicum ’s central carbon metabolism are likely more affected by concentrations of local substrates and allosteric metabolite effectors than by the concentration of enzymes. Recently, another systems biology study was performed in traditional non-substrate limited batch cultivations to investigate determinants of global regulation orchestrating the growth of C. glutamicum ( Haas et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Revisiting the Growth Modulon of Corynebacterium glutamicum Under Glucose Limited Chemostat Conditions

Graf

Haas

Teleki

et al. 2020

Front. Bioeng. Biotechnol.

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Increasing the growth rate of the industrial host Corynebacterium glutamicum is a promising target to rise productivities of growth coupled product formation. As a prerequisite, detailed knowledge about the tight regulation network is necessary for identifying promising metabolic engineering goals. Here, we present comprehensive metabolic and transcriptional analysis of C. glutamicum ATCC 13032 growing under glucose limited chemostat conditions with μ = 0.2, 0.3, and 0.4 h –1 . Intermediates of central metabolism mostly showed rising pool sizes with increasing growth. 13 C-metabolic flux analysis ( 13 C-MFA) underlined the fundamental role of central metabolism for the supply of precursors, redox, and energy equivalents. Global, growth-associated, concerted transcriptional patterns were not detected giving rise to the conclusion that glycolysis, pentose-phosphate pathway, and citric acid cycle are predominately metabolically controlled under glucose-limiting chemostat conditions. However, evidence is found that transcriptional regulation takes control over glycolysis once glucose-rich growth conditions are installed.

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The linkage between nutrient supply, intracellular enzyme abundances and bacterial growth: New evidences from the central carbon metabolism of Corynebacterium glutamicum

Cited by 13 publications

References 42 publications

Microbioreactor Systems for Accelerated Bioprocess Development

Microbioreactor Systems for Accelerated Bioprocess Development

Evolutionary engineering of Corynebacterium glutamicum

Revisiting the Growth Modulon of Corynebacterium glutamicum Under Glucose Limited Chemostat Conditions

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