Increase in arginine and citrulline production by 6-azauracil-resistant mutants of Bacillus subtilis

Kisumi, Masahiko; Takagi, Tsutomu; Chibata, Ichiro

doi:10.1128/aem.34.6.689-694.1977

Cited by 13 publications

(7 citation statements)

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“…Initial approach to produce ARG at industrial scale began with random mutagenesis of microorganisms (Table 1 ). Mutants selected based on their resistance to antimetabolites and other analogues such as canavanine (CVN) [ 40 ],[ 71 ], homoarginine [ 72 ], arginine hydroxamate (AHX) [ 18 ],[ 73 ], 6-azauracil (6 AU) [ 74 ], 2-thiazolealanine (TA) [ 75 ], and sulfaguanine (SG) [ 75 ] have been used in early attempts to overproduce ARG. Mutations were induced by radiation [ 75 ],[ 76 ] or treatment with mutagen such as N -methyl- N ’-nitro- N -nitrosoguanidine (NTG) [ 18 ],[ 75 ].…”

Section: Introductionmentioning

confidence: 99%

“…The rational for this is to confer higher tolerance of ARG to microorganisms and to remove feedback inhibition by ARG [ 9 ]. Historically, the random mutation approach had been used in various prokaryotic and eukaryotic strains including B. subtilis [ 18 ],[ 73 ],[ 74 ], Serratia marcescens [ 73 ], Micrococcus sodonensis [ 73 ], Norcadia corynebacteroides [ 73 ], N. rubra [ 73 ], Saccharomyces cerevisiae [ 73 ], Candida tropicalis [ 73 ] , C. glutamicum [ 72 ], C. crenatum [ 76 ], Brevibacterium flavum [ 75 ], B. ketoglutamicum [ 75 ], C. lilium [ 75 ], Arthrobacter paraffineus [ 75 ] and Microbacterium ammoniaphilum [ 73 ],[ 75 ] to produce ARG. The trend later shifted toward using GLU overproducing C. glutamicum strain and its related species C. crenatum as base strains, which led to industrial level ARG titers.…”

Section: Introductionmentioning

confidence: 99%

“…348 C. lilium NRRL B-2243 mutant; TA R 1.8 No. 352 B. flavum ATCC 14067 mutant; guanine auxotroph; TA R 34.8 1977 AAr-9 B. subtilis OUT 8103 mutant; 6AU R 28.0 [ 74 ] 1981 KY7690 B. subtilis ATCC 15244 mutant; AHX R , 5HUR R , TRA R , 6FTP R , 6AU R , 2TU R ; 5 liter bioreactor 14.0 [ 73 ] S. marcescens IFO 3046 mutant; AHX R , NIM R ; test tube culture 0.6 M. ammoniaphilum ATCC 15354 mutant; AHX R ; test tube culture 0.5 M. sodonensis ATCC 11880 mutant; AHX R ; test tube culture 4.0 N. corynebacteroides ATCC 14898 mutant; CVN R ; test tube culture 2.5 N. rubra NRRL 11094 mutant; AHX R ; test tube culture 8.0 2009 RBid C. glutamicum ATCC 13032, ΔargR , A26V/M31V in ArgB; 5 liter bioreactor 52.0 [ 47 ] 2009 SYPA 5-5 C. crenatum mutant; optimization of two-stage oxygen supply strategy; 5 liter bioreactor 36.6 [ 76 ] 2011 SYPA 5–5 (pJC- tac - vgb ) C. crenatum mutant, vector-based overexpression of vgb from Vitreoscilla 35.9 [ 77 ] 2011 SYPA 5–5 (pJC tac - argJ ) …”

Section: Introductionmentioning

confidence: 99%

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Metabolic engineering of microorganisms for the production of L-arginine and its derivatives

Shin

Lee

2014

Microb Cell Fact

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L-arginine (ARG) is an important amino acid for both medicinal and industrial applications. For almost six decades, the research has been going on for its improved industrial level production using different microorganisms. While the initial approaches involved random mutagenesis for increased tolerance to ARG and consequently higher ARG titer, it is laborious and often leads to unwanted phenotypes, such as retarded growth. Discovery of L-glutamate (GLU) overproducing strains and using them as base strains for ARG production led to improved ARG production titer. Continued effort to unveil molecular mechanisms led to the accumulation of detailed knowledge on amino acid metabolism, which has contributed to better understanding of ARG biosynthesis and its regulation. Moreover, systems metabolic engineering now enables scientists and engineers to efficiently construct genetically defined microorganisms for ARG overproduction in a more rational and system-wide manner. Despite such effort, ARG biosynthesis is still not fully understood and many of the genes in the pathway are mislabeled. Here, we review the major metabolic pathways and its regulation involved in ARG biosynthesis in different prokaryotes including recent discoveries. Also, various strategies for metabolic engineering of bacteria for the overproduction of ARG are described. Furthermore, metabolic engineering approaches for producing ARG derivatives such as L-ornithine (ORN), putrescine and cyanophycin are described. ORN is used in medical applications, while putrescine can be used as a bio-based precursor for the synthesis of nylon-4,6 and nylon-4,10. Cyanophycin is also an important compound for the production of polyaspartate, another important bio-based polymer. Strategies outlined here will serve as a general guideline for rationally designing of cell-factories for overproduction of ARG and related compounds that are industrially valuable.Electronic supplementary materialThe online version of this article (doi:10.1186/s12934-014-0166-4) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Metabolic engineering of microorganisms for the production of L-arginine and its derivatives

Shin

Lee

2014

Microb Cell Fact

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“…Scientists have been working to find a suitable strain for the production of arginine via fermentation of sugars since the early 1970s. Relatively high levels of arginine can be obtained by fermentation using Corynebacterium glutamicum or Corynebacterium crenatum strains. , These strains were used to produce arginine in concentrations ranging from 1.2 to 34.8 g/L in the 1970s and 1980s. − In 2009 and 2011, different groups reported high concentrations of arginine (between 45 and 52 g/L) using engineered C. gluamicum and C.…”

Section: Introductionmentioning

confidence: 99%

Recovery of l-Arginine from Model Solutions and Fermentation Broth Using Zeolite-Y Adsorbent

Faisal

Holmlund

Ginesy

et al. 2019

ACS Sustainable Chem. Eng.

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Arginine was produced via fermentation of sugars using the engineered microorganism Escherichia coli. Zeolite-Y adsorbents in the form of powder and extrudates were used to recover arginine from both a real fermentation broth and aqueous model solutions. An adsorption isotherm was determined using model solutions and zeolite-Y powder. The saturation loading was determined to be 0.2 g/g using the Sips model. Arginine adsorbed from a real fermentation broth using either zeolite-Y powder or extrudates both showed a maximum loading of 0.15 g/ g at pH 11. This adsorbed loading is very close to the corresponding value obtained from the model solution showing that under the experimental conditions the presence of additional components in the broth did not have a significant effect on the adsorption of arginine. Furthermore, a breakthrough curve was determined for extrudates using a 1 wt % arginine model solution. The selectivity for arginine over ammonia and alanine from the real fermentation broth at pH 11 was 1.9 and 8.3, respectively, for powder, and 1.0, and 4.1, respectively, for extrudates. To the best of our knowledge, this is the first time recovery of arginine from real fermentation broths using any type of adsorbent has been reported.

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“…Valine supplementation is of interest as valine often becomes limiting in low‐CP diets for piglets, and because valine deficiency has detrimental impact on animal growth performance (Milgen et al., ). B. subtilis is used as a probiotic in pig diets due to its positive effects on performance (Wang et al., ), and mutants of B. subtilis have been found to overproduce specific AA's (Kato, Kisumi, Takagi, & Chibata, ). The mutant strain B. subtilis ( B. subtilis VAL) overproduces Val in vitro (Nørgaard et al., ), and it was hypothesized that dietary supplementation of B. subtilis VAL would produce absorbable Val in situ by colonizing intestinal mucosa and/or digesta of pigs fed a Val‐deficient diet.…”

Section: Introductionmentioning

confidence: 99%

Transport of valine across the small intestinal epithelium in pigs fed different valine levels and Bacillus subtilis

Blaabjerg

Nørgaard

Nielsen

et al. 2017

Animal Physiology Nutrition

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Mutants of Bacillus subtilis overproducing valine (B. subtilis VAL) could be an approach to supply pigs dietary valine (Val). In the study, 18 gilts were fed: (i) negative diet with a standardized ileal digestible (SID) Val:Lys of 0.63:1 (Neg); (ii) Neg added B. subtilis VAL (1.28 × 10 cfu/kg as-fed) or; (iii) Neg added L-Val to a Val:Lys of 0.69:1. Using the Ussing chamber method, the study aimed to investigate whether (i) the diets affect intestinal transport of additions of 0, 5, 10 or 20 mmol Val/L from the mucosal to the serosal side and (ii) the B. subtilis VAL contributes to a net transport of Val produced in situ. The results showed that the Isc (ΔIsc ) and release of Val to the serosal side solution (S ; μmol cm min ) increased with Val addition (linear and quadratic, p < .0001) but was similar for 5, 10 or 20 mmol Val/L and not affected by diet. No net transport of in situ produced Val by B. subtilis VAL was detected. In conclusion, feeding a Val-deficient diet with or without B. subtilis VAL or a Val sufficient diet did not affect the Val transport across intestinal epithelia. No in situ Val production by B. subtilis VAL was observed in the Ussing chambers.

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Increase in arginine and citrulline production by 6-azauracil-resistant mutants of Bacillus subtilis

Cited by 13 publications

References 26 publications

Metabolic engineering of microorganisms for the production of L-arginine and its derivatives

Metabolic engineering of microorganisms for the production of L-arginine and its derivatives

Recovery of l-Arginine from Model Solutions and Fermentation Broth Using Zeolite-Y Adsorbent

Transport of valine across the small intestinal epithelium in pigs fed different valine levels and Bacillus subtilis

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