Production of l-lysine on different silage juices using genetically engineered Corynebacterium glutamicum

Neuner, Andreas; Wagner, Ines; Sieker, T.; Ulber, Roland; Schneider, Konstantin; Peifer, Susanne; Heinzle, Elmar

doi:10.1016/j.jbiotec.2012.07.190

Cited by 40 publications

(16 citation statements)

References 30 publications

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“…Downregulation of homoserine dehydrogenase (encoded by hom ) decreased the flux toward the competitive pathway [8, 44, 46]. Moreover, deletion of phosphoenolpyruvate carboxykinase (encoded by pck ) and upregulation of pyruvate carboxylase (encoded by pyc ) directed the flux toward oxaloacetate formation at the pyruvate node for l -lysine synthesis [8, 47]. Downregulation of aconitase (encoded by acn ) and isocitrate dehydrogenase (encoded by icd ) further minimized carbon loss from pyruvate [48].…”

Section: Resultsmentioning

confidence: 99%

A new genome-scale metabolic model of Corynebacterium glutamicum and its application

Zhang

Cai

Shang

et al. 2017

Biotechnol Biofuels

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Background Corynebacterium glutamicum is an important platform organism for industrial biotechnology to produce amino acids, organic acids, bioplastic monomers, and biofuels. The metabolic flexibility, broad substrate spectrum, and fermentative robustness of C. glutamicum make this organism an ideal cell factory to manufacture desired products. With increases in gene function, transport system, and metabolic profile information under certain conditions, developing a comprehensive genome-scale metabolic model (GEM) of C. glutamicum ATCC13032 is desired to improve prediction accuracy, elucidate cellular metabolism, and guide metabolic engineering.ResultsHere, we constructed a new GEM for ATCC13032, iCW773, consisting of 773 genes, 950 metabolites, and 1207 reactions. Compared to the previous model, iCW773 supplemented 496 gene–protein-reaction associations, refined five lumped reactions, balanced the mass and charge, and constrained the directionality of reactions. The simulated growth rates of C. glutamicum cultivated on seven different carbon sources using iCW773 were consistent with experimental values. Pearson’s correlation coefficient between the iCW773-simulated and experimental fluxes was 0.99, suggesting that iCW773 provided an accurate intracellular flux distribution of the wild-type strain growing on glucose. Furthermore, genetic interventions for overproducing l-lysine, 1,2-propanediol and isobutanol simulated using OptForceMUST were in accordance with reported experimental results, indicating the practicability of iCW773 for the design of metabolic networks to overproduce desired products. In vivo genetic modifications of iCW773-predicted targets resulted in the de novo generation of an l-proline-overproducing strain. In fed-batch culture, the engineered C. glutamicum strain produced 66.43 g/L l-proline in 60 h with a yield of 0.26 g/g (l-proline/glucose) and a productivity of 1.11 g/L/h. To our knowledge, this is the highest titer and productivity reported for l-proline production using glucose as the carbon resource in a minimal medium.ConclusionsOur developed iCW773 serves as a high-quality platform for model-guided strain design to produce industrial bioproducts of interest. This new GEM will be a successful multidisciplinary tool and will make valuable contributions to metabolic engineering in academia and industry.Electronic supplementary materialThe online version of this article (doi:10.1186/s13068-017-0856-3) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

A new genome-scale metabolic model of Corynebacterium glutamicum and its application

Zhang

Cai

Shang

et al. 2017

Biotechnol Biofuels

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“…Utilization of maltodextrins and even soluble starch with C. glutamicum has been achieved by expression of α-amylase (Seibold et al 2006;Tateno et al 2007). As novel cheap substrates, the utilization of xylose by C. glutamicum (Kawaguchi et al 2006), as well as arabinose (Meiswinkel et al 2013), methanol (Witthoff et al 2013), and further carbon sources (Buschke et al 2013;Neuner et al 2013) is under investigation.…”

Section: Sugar Uptakementioning

confidence: 99%

A giant market and a powerful metabolism: l-lysine provided by Corynebacterium glutamicum

Eggeling

Bott

2015

Appl Microbiol Biotechnol

207

106

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L-lysine is made in an exceptional large quantity of currently 2,200,000 tons/year and belongs therefore to one of the leading biotechnological products. Production is done almost exclusively with mutants of Corynebacterium glutamicum. The increasing L-lysine market forces companies to improve the production process fostering also a deeper understanding of the microbial physiology of C. glutamicum. Current major challenges are the identification of ancillary mutations not intuitively related with product increase. This review gives insights on how cellular characteristics enable to push the carbon flux in metabolism towards its theoretical maximum, and this example may also serve as a guide to achieve and increase the formation of other products of interest in microbial biotechnology.

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“…Apart from enabling access to alternative monomeric carbon sources that can be purified from agro‐ and industrial wastes, C. glutamicum has also been engineered for the utilization of polymers such as starch [68, 69] or glucans [70, 71]. Growth and synthesis of various bioproducts from rice straw and wheat bran hydrolysates [58, 72, 73] as well as grass juice [74] was shown.…”

Section: Realizing a Flexible Feedstock Concept: Access To Alternatmentioning

confidence: 99%

Engineering microbial cell factories: Metabolic engineering of Corynebacterium glutamicum with a focus on non‐natural products

Heider

Wendisch

2015

Biotechnology Journal

105

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Corynebacterium glutamicum is the workhorse of biotechnological amino acid production. For more than 50 years amino acid producing strains of this actinomycete have been improved by classical breeding, metabolic engineering and systems and synthetic biology approaches. This review focusses mainly on recent developments on C. glutamicum strain development for non-natural products. Recently, metabolite sensors have accelerated classical strain breeding. Synthetic pathways for access to alternative carbon sources, such as pentoses, and to new products, such as α, ω-amino acids, α, ω-diamines, α-keto acids, isobutanol, carotenoids and terpenes, have been embedded in the central metabolism of C. glutamicum. Furthermore, C. glutamicum is a chassis for new and improved production processes that has been improved in two ways: by rendering it biotin prototrophic and by curing it from its prophage DNA followed by further genome reduction. The first combinations of this chassis approach with production will be highlighted. Although their transfer to industrial scale processes will have to be evaluated, these recent achievements indicate how synthetic biology helps realizing proof-of-principles. Moreover, current and future synthetic biology technology developments hold the promise to explore the full potential of C. glutamicum as production host for value-added chemicals.

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Production of l-lysine on different silage juices using genetically engineered Corynebacterium glutamicum

Cited by 40 publications

References 30 publications

A new genome-scale metabolic model of Corynebacterium glutamicum and its application

A new genome-scale metabolic model of Corynebacterium glutamicum and its application

A giant market and a powerful metabolism: l-lysine provided by Corynebacterium glutamicum

Engineering microbial cell factories: Metabolic engineering of Corynebacterium glutamicum with a focus on non‐natural products

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