Metabolic engineering to guide evolution – Creating a novel mode for L-valine production with Corynebacterium glutamicum

Schwentner, Andreas; Feith, André; Münch, Eugenia; Busche, Tobias; Rückert, Christian; Kalinowski, Jörn; Blombach, Bastian

doi:10.1016/j.ymben.2018.02.015

Cited by 46 publications

(39 citation statements)

References 81 publications

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“…However, further studies are necessary to identify the molecular mechanisms underlying the activation of the glyoxylate shunt as a secondary effect of reduced ICD activity. In accordance with assumptions of Baumgart et al, the authors postulated that the reduced ICD activity and the resulting accumulation of isocitrate promote activation of the glyoxylate shunt . Based on a 1.9‐fold increased intracellular l ‐valine level and a predicted increased flux through the PDHC, Schwentner et al suggested that the re‐engineered strains represent promising candidates for l ‐valine producers.…”

Section: Metabolic Engineering To Guide Evolutionmentioning

confidence: 69%

“…Synthetic regulatory circuits can be constructed to couple intracellular product concentration to a selectable output, for example to fluorescent protein synthesis, which can be selected for by FACS, or to synthesis of an antibiotic or auxotrophic marker . Metabolic engineering to guide evolution can be applied to increase small molecule production by selecting for growth rate …”

Section: Metabolic Engineering To Guide Evolutionmentioning

confidence: 99%

“…Schwentner et al used the inactivation of anaplerotic reactions to evolve an alternative producer platform for the amino acid l ‐valine. This effort was motivated by the fact that metabolic engineering of C. glutamicum for l ‐valine production is typically based on complete inactivation or downregulation of the pyruvate dehydrogenase complex (PDHC) .…”

Section: Metabolic Engineering To Guide Evolutionmentioning

confidence: 99%

“…Whole genome sequencing of the evolved strains revealed icd , encoding isocitrate dehydrogenase (ICD), as a consistent mutation target in all evolved strains. Re‐engineering of the identified key mutations in icd revealed an upregulation of the glyoxylate shunt as an alternative route to replenish the oxaloacetate pool in the Δ pyc Δ ppc background . However, further studies are necessary to identify the molecular mechanisms underlying the activation of the glyoxylate shunt as a secondary effect of reduced ICD activity.…”

Section: Metabolic Engineering To Guide Evolutionmentioning

confidence: 99%

“…ALE has successfully been applied to increase the growth rate, substrate utilization, stress tolerance, and small molecule production . Growth coupling strategies have been used to increase precursor supply and small molecule production …”

Section: Introductionmentioning

confidence: 99%

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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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Section: Metabolic Engineering To Guide Evolutionmentioning

confidence: 69%

Section: Metabolic Engineering To Guide Evolutionmentioning

confidence: 99%

Section: Metabolic Engineering To Guide Evolutionmentioning

confidence: 99%

Section: Metabolic Engineering To Guide Evolutionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Evolutionary engineering of Corynebacterium glutamicum

Stella

Wiechert

Noack

et al. 2019

Biotechnology Journal

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Metabolic Engineering of Corynebacterium glutamicum

Becker

Wittmann

2021

Metabolic Engineering

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Optimization of CRISPR‐Cas9 through promoter replacement and efficient production of L‐homoserine in Corynebacterium glutamicum

Wang

et al. 2021

Biotechnology Journal

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Background Corynebacterium glutamicum is an important chassis for industrial applications. The low efficiency of commonly used genome editing methods for C. glutamicum limits the rapid multiple engineering of the bacterium. Main Methods and Major Results In this study, chromosome‐borne expression of cas9 and recET from Escherichia coli K12‐MG1655 was achieved to avoid toxicity to the strain, increase the probability of homologous recombination, and reduce loss of viability caused by double‐strand breaks. Constitutive strong promoters, such as P45, Ptrc, and PH36, were used to replace PglyA and to expand the application of the CRISPR‐Cas9 system. By using this system, a C. glutamicum strain producing L‐homoserine to 22.1 g per L in a 5‐L bioreactor after 96 h was obtained. Conclusions and Implications Through the application of visualized fluorescent protein, the process of plasmid curing was optimized, obtain a continuous and rapid CRISPR‐Cas9 genome editing system. The method described here could be useful to construct C. glutamicum mutant rapidly.

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Metabolic engineering to guide evolution – Creating a novel mode for L-valine production with Corynebacterium glutamicum

Cited by 46 publications

References 81 publications

Evolutionary engineering of Corynebacterium glutamicum

Evolutionary engineering of Corynebacterium glutamicum

Metabolic Engineering of Corynebacterium glutamicum

Optimization of CRISPR‐Cas9 through promoter replacement and efficient production of L‐homoserine in Corynebacterium glutamicum

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