• BMB Reports
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• v.28 no.3
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• pp.265-270
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• 1995

Acetolactate synthase (ALS, EC 4.1.3.18) is the first common enzyme in the biosynthesis of leucine, isoleucine, and valine. It is the target enzyme for several classes of herbicides, including the sulfonylureas, the imidazolinones, the triazolopyrimidines, the pyrimidyl-oxy-benzoates and the pyrimidyl-thio-benzens. The sulfonylurea-resistant ALS gene (SurB) from Nicotiana tabaccum [Lee et al. (1988) The EMBO J. 7, 1241-1248] was cloned into the bacterial expression plasmid pT7-7. The resulting recombinant plasmid pT7-ALS was used to transform an ALS-deficient Escherichia coli strain MF2000. MF2000 cells transformed with pT7-ALS grew in the absence of valine and isoleucine. ALS activities of 0.042 and 0.0002 ${\mu}mol/min/mg$ protein were observed in the crude extracts prepared from MF2000 cells transformed with plasmids pT7-ALS and pT7-7, respectively. In addition, the former crude extract containing mutant ALS was insensitive to inhibition by K11570, a new chemical class of herbicides. $IC_{50}$ values for K11570 were $0.13{\pm}0.01$ mM. For comparison, a plasmid pTATX containing the wild-type Arabidopsis thaliana ALS coding sequences was also expressed in MF2000. ALS activities of 0.037 ${\mu}mol/min/mg$ protein were observed, and the wild type ALS was sensitive to two different classes of herbicides, K11570 and ALLY, a sulfonylurea. $IC_{50}$ values for K11570 and ALLY were $0.63{\pm}0.07$ and $80{\pm}5.6$ nM, respectively. Thus, the results suggest that the sulfonylurea-resistant tobacco ALS was functionally expressed in the bacteria, and that K11570 herbicides bind to the regulatoty site of ALS enzymes.

• The Plant Pathology Journal
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• v.21 no.1
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• pp.77-82
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• 2005

A summer annual weed of monochoria (Monochoria vaginalis) grows in the edges of rice paddies, ditches, and moist upland throughout Korea. It is very difficult to control with herbicide because of its sulfonylurea resistance. It is very competitive with fast growing pattern, that can cause reducing yields of rice. Brown leaf blight of monochoria (Monochoria vaginalis) occurred naturally in rice paddy, is first reported in Korea. The fungal isolate BWC01-54 was successfully isolated from the diseased leaves of monochoria. The fungus BWC 01-54 was grown well at $25-28^{\circ}C$, conidia of the greysh black brown mycelia were abundant produced on PDA at 15 days. The fungus was grown well in potato dextrose broth at $28^{\circ}C$ and fully grown within 10 days in 250 ml of flask. In host and pathogenicity test, conidia suspension of BWC01-54 was the most effective to control of monochoria compare to others isolates. Typical symptoms having pin point brown lesions were formed on stem and leaf and which severely affected the whole plants ware blighted within two weeks, respectively. Under paddies field condition, conidial suspension of the fungus BWC01-54 gave around 90% control. Therefore, we conclude that the fungus may have a potential as a biological control agent against sulfonylurea resistance weed in rice paddy.

• Korean Journal of Clinical Pharmacy
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• v.28 no.3
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• pp.188-193
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• 2018

Background: Previous studies have noted that the simultaneous use of sulfonylureas and antimicrobials, which is common, could increase the risk of hypoglycemia. In particular, an age of 65 years or older is a known risk factor for sulfonylurea-related hypoglycemia in hospitalized patients. Therefore, we performed this study to determine the potential risk of hypoglycemia from the concurrent use of antimicrobials and sulfonylureas. Methods: We performed a cross-sectional study on the National Health Insurance Service-National Sample Cohort from 2013. The eligibility criteria included patients of 65 years of age or older taking a sulfonylurea with 25 different antimicrobials. Different risk ratings of severity in drug-drug interactions (potential DDIs), level X, D, or C in Lexi-$Interact^{TM}$ online, and contraindicated, major, or moderate severity level in $Micromedex^{(R)}$ were included. SAS version 9.4 was used for data analysis. Results: A total of 6,006 elderly patients with 25,613 prescriptions were included. The largest age group was 70 to 74 (32.7%), and 39.7% of patients were men. The mean number of prescriptions was 4.3 per patient. The most frequently used antimicrobials were levofloxacin (6,583, 25.7%), ofloxacin (6,549, 25.6%), fluconazole (4,678, 18.0%), and ciprofloxacin (2,551, 9.8%). Among sulfonylureas, glimepiride was prescribed most frequently, followed by gliclazide, glibenclamide, and glipizide. Conclusion: Of the antimicrobials with a high potential of hypoglycemia, levofloxacin, ofloxacin, fluconazole, and ciprofloxacin were used frequently. Thus, the monitoring of clinically relevant interactions is required for patients concurrently administered sulfonylureas and antimicrobials.

• BMB Reports
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• v.31 no.3
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• pp.287-295
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• 1998

Acetolactate synthase (ALS) is the first common enzyme in the biosynthesis of L-Ieucine, L-isoleucine, and L-valine. The sulfonylurea-resistant ALS gene from Nicotiana tabacum was cloned into the bacterial expression vector pGEX-2T. The resulting recombinant plasmid pGEX-ALS3 was used to transform Escherichia coli strain XL1-Blue, and the mutant tobacco ALS (mALS) was expressed in the bacteria as a protein fused with glutathione S-transferase (GST). The fusion product GST-mALS was purified in a single step on a glutathione-Sepharose column. ALS activities of 0.9-2.5 ${\mu}mol/min/mg$ protein were observed in the GST-mALS, and the Km values for pyruvate, FAD, and TPP were 10.8-24.1, $(1.9-8.9){\times}10^{-3}$, and 0.14-0.38 mM, respectively. The purified GST-mALS was resistant to both the sulfonylurea and the triazolopyrimidine herbicides, and lost its sensitivity to end products, L-valine and L-leucine. For comparision, the tobacco wild-type recombinant ALS fused with GST, GST-wALS, was also characterized with respect to its pyruvate and cofactor bindings. These results suggest that the purified mutant recombinant tobacco ALS was functionally active, that the mutations resulting in herbicide resistance has affected pyruvate and cofactor bindings," and that the two classes of herbicides interact at a common site on the plant ALS.

• Clinical and Experimental Pediatrics
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• v.54 no.4
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• pp.179-182
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• 2011

Transient neonatal diabetes mellitus (TNDM) is a rare form of diabetes mellitus that presents within the first 6 months of life with remission in infancy or early childhood. TNDM is mainly caused by anomalies in the imprinted region on chromosome 6q24; however, recently, mutations in the ABCC8 gene, which encodes sulfonylurea receptor 1 (SUR1), have also been implicated in TNDM. Herein, we present the case of a male child with TNDM whose mutational analysis revealed a heterozygous c.3547C>T substitution in the ABCC8 gene, leading to an Arg1183Trp mutation in the SUR1 protein. The parents were clinically unaffected and did not show a mutation in the ABCC8 gene. This is the first case of a de novo ABCC8 gene mutation in a Korean patient with TNDM. The patient was initially treated with insulin and successfully switched to sulfonylurea therapy at 14 months of age. Remission of diabetes had occurred at the age of 16 months. Currently, the patient is 21 months old and is euglycemic without any insulin or oral hypoglycemic agents. His growth and physical development are normal, and there are no delays in achieving neurological and developmental milestones.

• The Korean Journal of Pesticide Science
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• v.6 no.4
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• pp.320-323
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• 2002

New and fast degradable sulfonylurea derivaties possessing N-methylureido group were synthesized and their herbicidal effects were tested under the upland in greenhouse. N-methylureido benzenesulfonylureas showed better herbicidal activity against grass weeds than broad leaf weeds under post emergence.

• The Korean Journal of Pesticide Science
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• v.5 no.2
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• pp.33-36
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• 2001

New series of sulfonylureas containing substituted thiophene with 2-chloromethyl-1,3-dioxolane group were prepared, and their herbicidal effects were tested(in vivo) in the upland conditions and in the paddy submerged conditions. The sulfonylureas in which 4,6-dimethoxy- or 4-methyl-6-methoxy group in pyrimidine or triazine ring showed good herbicidal effects at a rate of 0.1 kg/ha. However, they showed weaker herbicidal effects than that of sulfonylureas containing substituted thiophene with 2-fluoromethyl-1,3-dioxolane group in general.

• The Korean Journal of Pesticide Science
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• v.11 no.4
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• pp.269-275
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• 2007

Four sulfonylurea(SU)-resistant Monochoria vaginalis(M. vaginalis) accessions were tested for levels of resistance to four SU herbicides which have been widely using in paddy fields of Korea, based on whole plant response and sensitivity of the target enzyme, acetolactate synthase(ALS). The resistant Naju, Nonsan and Gimje accessions were not affected to the survival by treatment with recommended dose of all SU herbicides tested. The $GR_{50}$ values for the Naju, Nonsan and Gimje accessions were 8- to 33-fold, 8- to 30-fold and 7- to 32-fold higher to recommended doses of all SU herbicides tested than the susceptible Cheongdo accession, respectively. However, the $GR_{50}$ values for Kimhae accession displayed an intermediate response and was only 4-to 13-fold more resistant than the susceptible accession. The ALS $I_{50}$ values for the Naju, Nonsan and Gimje accessions were 25- to 66-fold, 9- to 26-fold and 10- to 24-fold higher to recommended doses of all SU herbicides tested than the susceptible Cheongdo accession, respectively. However, the $I_{50}$ value for Kimhae accession was 4- to 9-fold more resistant than the susceptible accession, as determined by $I_{50}$ values of ALS.

• The Korean Journal of Pesticide Science
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• v.13 no.4
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• pp.290-297
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• 2009

This research aims to contribute the characterization of acetolactate synthase (Ec 4.1.3.18; ALS) and the resistance mechanism by sequence analysis of ALS gene of the sulfonylurea-resistant and -susceptible Monochoria vaginalis. The ALS gene was obtained from susceptible (S) and resistant (R) M. vaginalis to sulfonylurea herbicides (SUs). The 815 bp the fragment and the genomic DNA sequence coding for acetolactate synthase (ALS) of S and R biotypes of M. vaginalis were cloned and sequenced. Nineteen clones were divided greatly into 4 groups as result of sequencing. The first group was not difference to S type, the second group was amino acid of P197S which found point mutations causing substitution of serine for proline at amino acid 197, the third group was observed greatly other part of 6 places than group 1, and the fourth group appeared the intergrade of group 1 and 3. Therefore, it could be assumed what ALS gene of various types can be one plant. The peptide of the 13 amino acid Domain A region for ALS genes from R biotype of M. vaginalis differed from that of the S biotype by one base substitution at proline codon of Domain A. It could also be confirmed that point mutation of serine for proline at amino acid 197.

• The Korean Journal of Pesticide Science
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• v.10 no.4
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• pp.320-328
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• 2006

This study was conducted to evaluate the herbicidal efficacy of flucetosulfuron+pyrazosulfuron-ethyl against Eleocharis kuroguwai and Scirpus planiculmis and to investigate tank-mix of flucetosulfuron + pyrazosulfuron-ethyl with bentazone and 2,4-D to control sulfonylurea resistant Monochoria vaginalis and Scirpus juncoides. In controlling E. kuroguwai, flucetosulfuron + pyrazosulfuron-ethyl showed 75% control, lower than that (95%) of bentazone + MCPA, at 29 DAA (days after application), while at 60 DAA it showed 90%, greater than that of (78%) of bentazone + MCPA, with greater control than penoxsulam at all times. In case of Scirpus planiculmis control, flucetosulfuron + pyrazosulfuron-ethyl showed lower activity than bentazone + MCPA but greater than penoxsulam. Flucetosulfuron + pyrazosulfuron-ethyl showed consistently high activities against Echinochloa crus-galli and E. kuroguwai regardless of soil flooding condition, while penoxsulam and bentazone + cyhalofop showed significantly lower activity in 5 cm flooding condition than 0 cm flooding condition. Flucetosulfuron + pyrazosulfuron-ethyl did not control sulfonylurea resistant Monochoria vaginalis and Scirpus juncoides, while its tank-mix with bentazone or 2,4-D at 2/3 or 1/2-folds of their recommended rates, respectively, provided > 90% control.