Recent progress in development of synthetic biology platforms and metabolic engineering of Corynebacterium glutamicum

Woo, Han Min; Park, Jin Byung

doi:10.1016/j.jbiotec.2014.03.003

Cited by 49 publications

(27 citation statements)

References 116 publications

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“…) . Systematic engineering of metabolic pathways in C. glutamicum has allowed the biochemical production of novel products, such as platform chemicals (ethanol, ethylene glycol, glycolate, 3‐hydroxypropionic acid, 1,2‐propanediol, 1,3 propanediol, 2,3‐butanediol, and isobutanol) and polyamide monomers (putrescine, cadaverine, gamma‐aminobutyrate, 5‐aminovalerate, succinate, and glutarate) . Recently, extensive research has focused on the sustainable production of polyamide monomers using C. glutamicum owing to its ability to overproduce important amino acid precursors, i.e., l ‐lysine and l ‐glutamate .…”

Section: Introductionmentioning

confidence: 99%

Recent advances in metabolic engineering of Corynebacterium glutamicum as a potential platform microorganism for biorefinery

Baritugo

Kim

David

et al. 2018

Biofuels Bioprod Bioref

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The fermentative production of platform chemicals in biorefineries is a sustainable alternative to current petroleum‐refining processes. Industrial microorganisms, such as Escherichia coli, Saccharomyces cerevisiae, and Corynebacterium glutamicum, have been engineered as microbial cell factories that are able to utilize biomass for the production of value‐added platform chemicals and polymers. Compared to E. coli and S. cerevisiae, C. glutamicum displays weak carbon catabolite repression and can co‐utilize mixed sugars as carbon sources, without any significant growth retardation. Pathways for the utilization of alternative carbon sources, such as d‐xylose and l‐arabinose from lignocellulosic biomass, lactose and galactose from whey, glycerol from biodiesel, and methanol from natural gas refineries, have been evaluated for chemical production. However, the application of C. glutamicum in biorefineries is limited because it does not secrete hydrolases for the efficient utilization of cellulose, xylan, and starch from lignocellulosic and starch biomass. To solve the limitation, C. glutamicum has been engineered for the consolidated bioprocessing of biomass by the heterologous expression of amylolytic and cellulolytic enzymes. Recently, C. glutamicum has been extensively engineered for polyamide monomer production owing to its ability to produce l‐lysine and l‐glutamate. This review summarizes recent advances in the development of C. glutamicum strains that can utilize renewable biomass resources for the production of industrially important chemicals. It highlights recent progress in metabolic engineering for the production of polyamide monomers. © 2018 Society of Chemical Industry and John Wiley & Sons, Ltd

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Section: Introductionmentioning

confidence: 99%

Recent advances in metabolic engineering of Corynebacterium glutamicum as a potential platform microorganism for biorefinery

Baritugo

Kim

David

et al. 2018

Biofuels Bioprod Bioref

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“…Classical mutagenesis and selection [169], overcoming allosteric feedback inhibition of key enzymes [170, 171], and metabolic engineering, like e.g. engineering of cofactor availability [172], have been combined with systems biology [173–177], omics analyses such as transcriptome sequencing [178] and quantitative proteomics [179] and the respective high‐throughput screening [180]. As reviewed here, synthetic biology approaches have been applied to C. glutamicum strain development with two aims: (i) embedding synthetic pathways into the host metabolism to generate new function, e.g.…”

Section: Concluding Remarks and Outlookmentioning

confidence: 99%

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

Heider

Wendisch

2015

Biotechnology Journal

104

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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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“…C. glutamicum is used in industrial biotechnology to produce several million tons of L-amino acids, such as the flavor enhancer L-glutamate (2,300,000 t/year) and the feed additive L-lysine (1,600,000 t/year) annually (Becker et al, 2011;Chen et al, 2014;Woo and Park, 2014). Thus, C. glutamicum has become a platform organism in industrial biotechnology .…”

Section: Introductionmentioning

confidence: 99%

“…Although this classical approach has been successful in terms of improving the yield of L-leucine by genetic manipulation of C. glutamicum; it has some limitations. The genetic alterations caused by random mutagenesis includes the region which is not directly related to amino acid biosynthesis, thereby causing some unwanted changes in cellular physiology such as, growth retardation and byproduct formation (Woo and Park, 2014). In particular, the accumulation of large amounts of by-products is a problem in the production of the three BCAAs due to their overlapping biosynthetic pathways, which negatively affects the yield and downstream processing.…”

Section: Introductionmentioning

confidence: 99%

Metabolic engineering of Corynebacterium glutamicum to enhance L-leucine production

Huang¹,

Liang²,

Wu³

et al. 2017

Afr. J. Biotechnol.

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This work aimed to develop an efficient L-leucine industrial production strain of Corynebacterium glutamicum by using metabolic engineering. A recombinant C. glutamicum strain was constructed by expressing a feedback-resistant leuA-encoded 2-isopropylmalate synthase (IPMS) that carries three amino acid exchanges (R529H, G532D and L535V) from the mutant strain C. glutamicum ML1-9 which was obtained by screening for structural analogues. In order to improve the expression of IPMS, a strong promoter (tac promoter) was used to ensure efficient expression of the rate-limiting enzyme. In addition, reasonable metabolic modifications on the central carbon metabolic pathway and competitive metabolic pathways to optimize the L-leucine biosynthesis pathway by redistribution of various types of precursors and repression of negative regulation were used aimed for increased L-leucine production. The modifications involved (1) deletion of the gene encoding the repressor LtbR to increase expression of leuBCD, (2) deletion of the gene encoding the AlaT to decrease the concentration of extracellular L-alanine, and increased availability of pyruvate for L-leucine formation, (3) deletion of the gene encoding the threonine dehydratase to abolish L-isoleucine synthesis and to eliminate the intermediate precursor of L-isoleucine biosynthesis competing with L-leucine biosynthesis, (4) inactivation of the pantothenate synthetase to increase α-ketoisovalerate formation, and to enable its further conversion to L-leucine, and (5) inactivation of lactate dehydrogenase to decrease lactate production and its pyruvate consumption, concomitant to decreased glucose consumption rates and prevention of lactic acid to restrict cell growth. The production performance of the engineered strain MDLeu-19/pZ8-1leuA r was characterized with cultivations in a bioreactor. Under fed-batch conditions in a 50-L automated fermentor, the best producer strain accumulated 38.1 g L -1 of L-leucine; the molar product yield being 0.42 mol L-leucine per mole of glucose (glucose conversion rate attained 26.4%). Moreover, during large-scale fermentation using a 150-m 3 fermentor, this strain produced more than 37.5 g L -1 L-leucine and the glucose conversion rate was 25.8%, making this process potentially viable for industrial production.

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Recent progress in development of synthetic biology platforms and metabolic engineering of Corynebacterium glutamicum

Cited by 49 publications

References 116 publications

Recent advances in metabolic engineering of Corynebacterium glutamicum as a potential platform microorganism for biorefinery

Recent advances in metabolic engineering of Corynebacterium glutamicum as a potential platform microorganism for biorefinery

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

Metabolic engineering of Corynebacterium glutamicum to enhance L-leucine production

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