Metabolic engineering of Corynebacterium glutamicum for L-arginine production

Park, Seok Hyun; Kim, Hyun Uk; Kim, Tae Yong; Park, Jun Seok; Kim, Suok-Su; Lee, Sang Yup

doi:10.1038/ncomms5618

Cited by 219 publications

(132 citation statements)

References 32 publications

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“…Metabolic engineering led to high production of L-arginine (Jensen et al 2015;Park et al 2014;Schneider et al 2011), a semi-essential amino acid with applications in the cosmetic, pharmaceutical, and food industries (Ikeda et al 2009;Park et al 2014). LysE and ArgO are known as L-arginine exporters of C. glutamicum and E. coli, respectively (Bellmann et al 2001;Nandineni and Gowrishankar 2004).…”

Section: Introductionmentioning

confidence: 99%

Roles of export genes cgmA and lysE for the production of l-arginine and l-citrulline by Corynebacterium glutamicum

Lubitz

Jorge

Pérez-García

et al. 2016

Appl Microbiol Biotechnol

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L-arginine is a semi-essential amino acid with application in cosmetic, pharmaceutical, and food industries. Metabolic engineering strategies have been applied for overproduction of L-arginine by Corynebacterium glutamicum. LysE was the only known L-arginine exporter of this bacterium. However, an L-arginine-producing strain carrying a deletion of lysE still accumulated about 10 mM L-arginine in the growth medium. Overexpression of the putative putrescine and cadaverine export permease gene cgmA was shown to compensate for the lack of lysE with regard to L-arginine export. Moreover, plasmid-borne overexpression of cgmA rescued the toxic effect caused by feeding of the dipeptide Arg-Ala to lysE-deficient C. glutamicum and argO-deficient Escherichia coli strains. Deletion of the repressor gene cgmR improved L-arginine titers by 5 %. Production of L-lysine and L-citrulline was not affected by cgmA overexpression. Taken together, CgmA may function as an export system not only for the diamine putrescine and cadaverine but also for L-arginine. The major export system for L-lysine and L-arginine LysE may also play a role in L-citrulline export since production of L-citrulline was reduced when lysE was deleted and improved by 45 % when lysE was overproduced.

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Section: Introductionmentioning

confidence: 99%

Roles of export genes cgmA and lysE for the production of l-arginine and l-citrulline by Corynebacterium glutamicum

Lubitz

Jorge

Pérez-García

et al. 2016

Appl Microbiol Biotechnol

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“…It can also be used as animal feed or fertilizer [2]. Corynebacterium glutamicum and C. crenatum have been commonly used for the microbial production of L-arginine [3][4][5][6]. Environmental concerns prompt a sustainable use of raw materials that are widely available, easily renewable, and that do not compete with food production.…”

Section: Introductionmentioning

confidence: 99%

Tuning of the Carbon-to-Nitrogen Ratio for the Production of l-Arginine by Escherichia coli

Ginesy

Rusanova-Naydenova

2017

Fermentation

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L-arginine, an amino acid with a growing range of applications within the pharmaceutical, cosmetic, food, and agricultural industries, can be produced by microbial fermentation. Although it is the most nitrogen-rich amino acid, reports on the nitrogen supply for its fermentation are scarce. In this study, the nitrogen supply for the production of L-arginine by a genetically modified Escherichia coli strain was optimised in bioreactors. Different nitrogen sources were screened and ammonia solution, ammonium sulphate, ammonium phosphate dibasic, and ammonium chloride were the most favourable nitrogen sources for L-arginine synthesis. The key role of the C/N ratio for L-arginine production was demonstrated for the first time. The optimal C/N molar ratio to maximise L-arginine production while minimising nitrogen waste was found to be 6, yielding approximately 2.25 g/L of L-arginine from 15 g/L glucose with a productivity of around 0.11 g/L/h. Glucose and ammonium ion were simultaneously utilized, showing that this ratio provided a well-balanced equilibrium between carbon and nitrogen metabolisms.

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“…orynebacterium glutamicum represents one of the most important biotechnological platform organisms and massively contributes to the industrial production of amino acids (1)(2)(3)(4)(5), but it has also been engineered, for instance, for the production of lower alcohols (6)(7)(8)(9), organic acids (10-13), diamines (14,15), and carotenoids (16)(17)(18). However, currently applied expression setups show only moderate performance regarding both precise control and expression homogeneity.…”

mentioning

confidence: 99%

Light-Controlled Cell Factories: Employing Photocaged Isopropyl-β- d -Thiogalactopyranoside for Light-Mediated Optimization of lac Promoter-Based Gene Expression and (+)-Valencene Biosynthesis in Corynebacterium glutamicum

Binder

Frohwitter

Mahr

et al. 2016

Appl Environ Microbiol

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Precise control of microbial gene expression resulting in a defined, fast, and homogeneous response is of utmost importance for synthetic bio(techno)logical applications. However, even broadly applied biotechnological workhorses, such as Corynebacterium glutamicum, for which induction of recombinant gene expression commonly relies on the addition of appropriate inducer molecules, perform moderately in this respect. Light offers an alternative to accurately control gene expression, as it allows for simple triggering in a noninvasive fashion with unprecedented spatiotemporal resolution. Thus, optogenetic switches are promising tools to improve the controllability of existing gene expression systems. In this regard, photocaged inducers, whose activities are initially inhibited by light-removable protection groups, represent one of the most valuable photoswitches for microbial gene expression. Here, we report on the evaluation of photocaged isopropyl-␤-D-thiogalactopyranoside (IPTG) as a light-responsive control element for the frequently applied tac-based expression module in C. glutamicum. In contrast to conventional IPTG, the photocaged inducer mediates a tightly controlled, strong, and homogeneous expression response upon short exposure to UV-A light. To further demonstrate the unique potential of photocaged IPTG for the optimization of production processes in C. glutamicum, the optogenetic switch was finally used to improve biosynthesis of the growth-inhibiting sesquiterpene (؉)-valencene, a flavoring agent and aroma compound precursor in food industry. The variation in light intensity as well as the time point of light induction proved crucial for efficient production of this toxic compound. IMPORTANCEOptogenetic tools are light-responsive modules that allow for a simple triggering of cellular functions with unprecedented spatiotemporal resolution and in a noninvasive fashion. Specifically, light-controlled gene expression exhibits an enormous potential for various synthetic bio(techno)logical purposes. Before our study, poor inducibility, together with phenotypic heterogeneity, was reported for the IPTG-mediated induction of lac-based gene expression in Corynebacterium glutamicum. By applying photocaged IPTG as a synthetic inducer, however, these drawbacks could be almost completely abolished. Especially for increasing numbers of parallelized expression cultures, noninvasive and spatiotemporal light induction qualifies for a precise, homogeneous, and thus higher-order control to fully automatize or optimize future biotechnological applications. Corynebacterium glutamicum represents one of the most important biotechnological platform organisms and massively contributes to the industrial production of amino acids (1-5), but it has also been engineered, for instance, for the production of lower alcohols (6-9), organic acids (10-13), diamines (14, 15), and carotenoids (16-18). However, currently applied expression setups show only moderate performance regarding both precise control and expression homogene...

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Metabolic engineering of Corynebacterium glutamicum for L-arginine production

Cited by 219 publications

References 32 publications

Roles of export genes cgmA and lysE for the production of l-arginine and l-citrulline by Corynebacterium glutamicum

Roles of export genes cgmA and lysE for the production of l-arginine and l-citrulline by Corynebacterium glutamicum

Tuning of the Carbon-to-Nitrogen Ratio for the Production of l-Arginine by Escherichia coli

Light-Controlled Cell Factories: Employing Photocaged Isopropyl-β- d -Thiogalactopyranoside for Light-Mediated Optimization of lac Promoter-Based Gene Expression and (+)-Valencene Biosynthesis in Corynebacterium glutamicum

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