• BMB Reports
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• v.39 no.1
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• pp.9-15
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• 2006

To prove whether error catastrophe /lethal mutagenesis is the primary antiviral mechanism of action of ribavirin against foot-and-mouth disease virus (FMDV). Ribavirin passage experiments were performed and supernatants of $Rp_1$ to $Rp_5$ were harvested. Morphological alterations as well as the levels of viral RNAs, proteins, and infectious particles in the BHK-21 cells infected using the supernatants of $Rp_1$ to $Rp_5$ and control were measured by microscope, real-time RT-PCR, western-blotting and plaque assays, respectively. The mutation frequency was measured by sequencing the complete P1- and 3D-encoding region of FMDV after a single round of virus infection from ribavirin-treated or untreated FMDV-infected cells. Ribavirin treatment for FMDV caused dramatically inhibition of multiplication in cell cultures. The levels of viral RNAs, proteins, and infectious particles in the BHK-21 cells infected were more greatly reduced along with the passage from $Rp_1$ to $Rp_5$, moreover, nucleocapsid protein could not be detected and no recovery of infectious virus in the supernatant or detection of intracellular viral RNA was observed at the $Rp_5$-infected cells. A high mutation rate, giving rise to an 8-and 11-fold increase in mutagenesis and resulting in some amino acid substitutions, was found in viral RNA synthesized at a single round of virus infection in the presence of ribavirin of $1000\;{\mu}M$ and caused a 99.7% loss in viral infectivity in contrast with parallel untreated control virus. These results suggest that the antiviral molecular mechanism of ribavirin is based on the lethal mutagenesis/error catastrophe, that is, the ribavirin is not merely an antiviral reagent but also an effective mutagen.

• 한국생물공학회:학술대회논문집
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• 2000.04a
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• pp.299-302
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• 2000

Actinoplanes teichomyceticus ATCC 31121 was mutated with UV to obtain a superior mutant strain with increasing level of teicoplanin production. In this investigation lethal curve was obtained and the optimal condition to induce mutagenesis was determined and to isolate the desirable mutant strain. It was also confirmed that teicoplanin activities by agar diffusion method to be compared to the mother strain. One mutant strain, T991014-1 that had the highest teicoplanin productivity was finally selected for further investigation including fermentation pattern. The mutant was characterized by the various tests such as amylase activity, protease activity, antibiotic resistance, autotoxicity, and productivity.

• Journal of Life Science
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• v.7 no.1
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• pp.49-58
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• 1997

Single P[en-lacZ] element including 5.7 kb of engrailed upstream sequences and the E. coli lacZ fusion gene, localized on 48A in rxyho25 strain was transposed to different sites in the Drosophila genome by the jumpstart technique. From 3315 individual genetic crosses, 113 new insertion lines carrying P[en-lacZ] inserted at different sites were obtained. $\beta$-Galactosidase expression in larval tissues of 113 insertion lines were detected by X-gal staining. & among 113 lines have been indentified to be for recessive lethal mutations. Among 7 lines, the #1119 line being lethal during embryogenesis was examined about the ${\beta}$$-Galactosidase expression, nuclear behavior and cellularization pattern during embryogenesis. The P[en-lacZ] insertion lines obtained in this study could be utilized for studying structure and function of the Drosophila development-related genes.

• Korean Journal of Microbiology
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• v.25 no.1
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• pp.57-66
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• 1987

Mutants of E. coli which showed increased sensitivity to MMS(methylmethane sulfonate)were isolated by MNNG mutagenesis and characterized by enzymatic assay, survival of simple alkylating agents and host-cell reactivation. E.coli mutant, 5-62, which showed absolute deficiency in 3-methyladenine DNA glycosylase II activity and had low capability of reactivating MMS-treated phage charon 35 was very sensitive to MMS and MNNG. NNS gene which confered resistance to the lethal effects of MMS was cloned in 5-62 strain. 5-62 mutants carrying recombinant plasmid, pMRG 1, which acquired resistance to the lethal effects of MMS had normal sensitivity to MNNG. Resistance to MMS was somewhat increased after they were treated with 0.5.$\mu$g MNNG/ml for 2 hours at $37^{\circ}C$. Although recombinant plasmid, pMRG 1, did not complement alk A mutation in 5-62 and ada mutation in 1-27 mutnat, mutnats transformed with this plasmid showed more capability of reactivating MMS treated phage than mutants.

• Fisheries and Aquatic Sciences
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• v.15 no.2
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• pp.145-150
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• 2012

An improved strain of the red seaweed Porphyra suborbiculata containing an increased amount of the essential amino acid L-lysine was obtained through mutation and analog enrichment. Mutagenesis using a 10% lethal dose of ultraviolet irradiation and an enrichment culture with the L-lysine analog aminoethyl-L-cysteine (AEC) was repeated to select the most productive strain using monospores of P. suborbiculata. The concentrations of AEC required to produce 50 and 100% inhibition of survival were 60 and 115 mM in the parent strain, and 72 and 135 mM in the selected AEC-resistant strain, respectively. The AEC-resistant strain, L130, produced 1.74-fold more lysine compared to its parent strain. Thus, mutagenesis with analog enrichment shows promise for selecting seaweed strains that can overproduce this essential amino acid.

• Korean Journal of Microbiology
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• v.37 no.4
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• pp.299-304
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• 2001

Teicoplanin is a kind of glycopeptide antibiotics produced by Actinoplanes teichomyceticus, and used in the clinical antibiotic such as vancomycin against methicillin-resistant Stabphylococcus aureus (MRSA). Actino planes teichomyceticus ATCC 31121 was mutated with UV to obtain a superior mutant strain with increased level of teicoplanin production. In this investigation, lethal curve was obtained and the optimal condition to induce mutagenesis was determined to isolate the desirable mutant strain. It was also confirmed that teicoplanin activities by agar diffusion method was compared with the parent strain. One mutant strain, T991014-1 with the highest productivity, was finally selected, and was characterized through the various tests such as amylase activity, protease activity, halotolerance, antibiotic resistance, autotoxicity, and productivity. Ad fermentation characteristics of the mutant strain were also studied.

• Journal of Plant Biotechnology
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• v.45 no.1
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• pp.55-62
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• 2018

In the present study in vitro mutagenesis was used to study the effect of gamma irradiation and EMS on callus induction, morphogenesis and production of multiple shoots from different explants of Citrullus colocynthis (L.) Schrad. Gamma radiations (5 kR to 20 kR) and certain chemicals have been effected on plant growth developments and changes of biochemical metabolisms in plants. Murashige and Skoog (MS) medium containing with auxins such as NAA, IAA, 2,4-D (0.5 ~ 2.0 mg/l), cytokinines BAP, kn TDZ, (0.5 ~ 2.5 mg/l), L-Glutamic acid (1 ~ 2 mg/l) and Coconut milk (10 ~ 20%). After 5 weeks on induction media, explants and callus (EC) were exposed to 5 kR, 10 kR, 15 kR and 20kR, of gamma radiation and treated with 1, 2, 3, 4 and 5 mM ethyl methane sulphonate (EMS) for 30 min. The highest percentage of callusing was observed (70%) stem irradiated with 5 kR and significantly decrease in fresh and dry weight of callus in the below 4 kR doses and above 20 kR doses, there was a progressive decrease in the fresh weight and dry weights when compared to control callus. Maximum percentage of plantlet regeneration (59%) was induced from callus exposed to 15 kR gamma irradiation on MS media fortified with 2.0 mg/l 2,4-D + 2.0 mg/l BAP + 2.0 mg/l L-glutamic acid. Increase in gamma irradiation dose above 15 kR and 5 mM EMS reduced regeneration capacity of callus. Doses higher than 20 kR and 7 mM EMS was lethal to micropropagated plants of Citurullus colocynthis.

• Journal of Environmental Science International
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• v.1 no.2
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• pp.1-13
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• 1992

Physiological toxic and mutagenic effects of gramoxone in Drosophila melanogaster were invetigated. Gramoxone was highly toxic on the development, resulting in of lowering the viability and in prolongation of the developmental times. Adults treated with gramoxone during the developmental stages caused a lowering of the productivity and a little chinge in protein quantity. But the effect on the sex-linked lethal mutagenesis was found to be negative. The order of mortality causing ado리t stoa형e feeding to gramoxone in the D. melanogaster complex was like this ; D. mauritiana, D. sechellia, D. simulans and D. melanogasteu Two species of the D. yakuba complex were alike. Those results were more or less correlation with speciation of the D. melanogaster subgroup.

• BMB Reports
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• v.38 no.1
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• pp.89-96
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• 2005

Earlier, we reported that the bacteriophage $\lambda$ P gene product is lethal to Escherichia coli, and the E. coli rpl mutants are resistant to this $\lambda$ P gene-mediated lethality. In this paper, we show that under the $\lambda$ P gene-mediated lethal condition, the host DNA synthesis is inhibited at the initiation step. The rpl8 mutation maps around the 83 min position in the E. coli chromosome and is 94% linked with the dnaA gene. The rpl8 mutant gene has been cloned in a plasmid. This plasmid clone can protect the wild-type E. coli from $\lambda$ P gene-mediated killing and complements E. coli dnaAts46 at $42^{\circ}C$. Also, starting with the wild-type dnaA gene in a plasmid, the rpl-like mutations have been isolated by in vitro mutagenesis. DNA sequencing data show that each of the rpl8, rpl12 and rpl14 mutations has changed a single base in the dnaA gene, which translates into the amino acid changes N313T, Y200N, and S246T respectively within the DnaA protein. These results have led us to conclude that the rpl mutations, which make E. coli resistant to $\lambda$ P gene-mediated host lethality, are located within the DNA initiator gene dnaA of the host.

• BMB Reports
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• v.42 no.5
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• pp.260-264
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• 2009

Tumor necrosis factor-$\alpha$ (TNF-$\alpha$) exhibits cytotoxicity towards various tumor cells in vitro and induces apoptotic necrosis in transplanted tumors in vivo. It also shows severe toxicity when used systemically for the treatment of cancer patients, hampering the development of TNF-$\alpha$ as a potential anticancer drug. In order to understand the structure-function relation of TNF-$\alpha$ with respect to receptor binding, we selected four regions on the bottom of the TNF-$\alpha$ trimer that are in close contact with the receptor and carried out mutagenesis studies and computational modeling. From the study, various TNF-$\alpha$ muteins with a high therapeutic index were identified. These results will provide a structural basis for the design of highly potent TNF-$\alpha$ for therapeutic purposes. By conjugating TNF-$\alpha$ muteins with a high therapeutic index to a fusion partner, which targets a marker of angiogenesis, it could be possible to develop TNF-$\alpha$ based anticancer drugs.