• 한국환경과학회지
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• 제17권2호
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• pp.249-255
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• 2008

The experiment was conducted to determine effect of the mixed herbal medicine for the substitution of antibiotics on the performance of laying hens. Day old hyline 1,500 layer chicks were randomly assigned to 4 treatments. Control were 600 chicks and there were three treatments of each 300 chicks. The 4 treatments were as follows: the mixed herbal medicine 0.1%(T-1), 0.3%(T-2) and 0.5%(T-3) after removed antibiotics on commercial feed and commercial feed( control) from 5th week to 13th week, each treatment was replicated 3 times and from 14th week to 18th week. Each 100 hens of the mixed herbal medicine 0.1%(CT-1), 0.3%(CT-2) and 0.5%(CT-3) were moved to cage. Body weight were measured on 4th, 8th, 13th week and feed intake, mortality were measured on every weeks. Body weight at fourth week, all treatments tended to be higher than control and T-3 statistically was highest(p<0.01). On 8th week, also treatments statistically high and T-1 was highest(p<0.01). But 12th week, there was not significantly different among treatments. Therefore it will be possible that the mixed herbal medicine substitute for antibiotics after vaccination. Mortality was not different between treatment and control overall rearing period. Early laying period($19{\sim}41wk$), T-2 showed highest feed intake(107.1g) among treatments, later laying period($42{\sim}77wk$), T-1 showed highest feed intake(134.3g) and was not any different among each treatments.

• 한국환경과학회지
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• 제17권5호
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• pp.537-546
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• 2008

The experiment was conducted to determine the effect of the mixed herbal medicine for the substitution of antibiotics on the performance of laying hens. Day old hyline 1,500 layer chicks were randomly assigned to 4 treatments. Control were 600 and three each treatment was 300. Eggs were collected at every weeks for measuring egg production and week 26, 27, 28 for chemical analyses. Chemical analyses were done for fatty acid profile of egg yolks, amino acid, antibiotics residue in eggs(collect eggs after supplying OTC 21ppm/bird/day to control for four day at 26, 27, 28) during the laying period($19{\sim}77wk$). On $0{\sim}4$ week, T-3 showed higher feed intake than those fed the other diets and on $5{\sim}13$ week, T-2 showed highest feed intake among treatments. After birds were moved ($14{\sim}18$ wk) CT-3 showed highest, but for overall rearing period, there was not significantly different among treatments. In conclusion the mixed herbal medicine did not tended to influence palatability to rearing birds. Egg quality(egg yolk color, haugh unit, eggshell breaking strength) showed no difference among treatments. Ratio of unsaturated fatty acid (mg/100g)/saturated fatty acid (mg/100g) was not difference among treatments, but linolenic acid and docosahexaenoic acid(DHA) of the mixed herbal medicine treatments showed higher then control. The antibiotics residue of CT, T treatments egg was not detected and control was not detected or below allowance. In conclusion the mixed herbal medicine can be possible to feed laying hen without antibiotics.

• KDI Journal of Economic Policy
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• 제30권2호
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• pp.129-155
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• 2008

급성상기도감염증에 대한 항생제 처방률은 의료기관의 유형, 표시과목, 의료기관이 위치한 지역 등 여러 요인에 따라 차이를 보인다. 본 연구는 1차 의료기관인 의원들 중 내과, 소아과, 이비인후과 의원의 급성상기도감염증에 대한 항생제 처방률에 환자의 특성과 같은 의학적 요인이 아닌 의원의 수입과 밀접한 관계가 있는 의원 수의 변화(경쟁 정도의 변화)와 같은 경제적 요인이 미치는 영향을 실증 분석하였다. 2006년 건강보험심사평가원에서 발표한 전국 각 의료기관의 급성상기도감염증에 대한 항생제 처방률을 주 자료원으로 하여, 경쟁지수를 두 가지 형태로 정의하고 수요 측면을 나타내는 변수와 공급 측면을 나타내는 변수를 통제변수로 선정하여 회귀분석을 실시한 결과 경쟁지수를 어떤 형태로 정의하든, 의원이 위치한 지역의 경쟁정도는 의사들의 항생제 처방률에 통계적으로 유의한 영향을 미친 것으로 분석되었다. 이러한 결과는 시장지역 내 경쟁 정도의 변화와 같은 경제적 요인이 의사들의 처방행태에 영향을 미치는 요인 중 하나라고 해석할 수 있다. 아울러 인과관계의 방향과 관련하여, 의사가 진료하는 지역의 경쟁 정도가 높아질수록 항생제 처방률이 통계적으로 유의하게 높아지는 것으로 나타났다. 이러한 결과는 의사의 진료수입 감소를 초래할 것으로 예상되는 시장환경의 변화에 대해 자신의 진료수입을 예전상태로 보전하기 위해 불필요한 의료서비스 소비를 유도해서 얻는 편익(소득효과)이 이를 위해 자신이 지불해야 할 비용(대체효과)보다 크기 때문에 항생제 처방률을 증가시킨 것으로 해석할 수 있으며, 또한 경제적 유인체계의 변화에 대하여 의사의 진료행태가 영향을 받을 수 있음을 실증적으로 뒷받침하는 것으로 이해할 수 있을 것이다.

• 한국축산시설환경학회지
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• 제17권1호
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• pp.1-10
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• 2011

본 연구는 설문지를 이용하여 한우사육 114농가를 대상으로 2010년 5~6월까지 조사하였다. 동물약품이용실태를 파악하고, 항생제 규제에 따른 대체제 이용방향 등을 통하여 한우농가에 필요한 동물약품 사용과 연구에 기초적 자료를 제공하고자 실시되었으며, 그 결과를 요약하면 다음과 같다. 전체 한우농가에서 가장 선호하는 동물약품 종류는 생균제 (40.4%)로 나타났으며, 그 다음으로는 항생제류 (28.1%), 백신류 (19.3%), 면역제제류 (12.3%) 순으로 나타났다. 지역별 (p<0.05)과 농가규모별 (p<0.05) 동물약품 선호도에서 각각 유의한 차이를 보였는데, 이는 지역이나 규모에 따라 관행적 사용에 기인한 것으로 나타났다. 동물약품 선택 시 고려요인으로는 효능 (31.6%), 가격 (19.3%), 환경 (17.5%), 부작용 (15.8%) 순으로 나타났다. 지역별로는 선택기준이 유의성있는 차이가 인정되었으나 (p<0.05), 사육규모별에서는 유의성있는 차이가 나타나지 않았다 (p>0.05). 동물약품구입경로에 대한 조사에서는 관납(41.6%)이 가장 많았으며, 동물약국 (30.7%), 수의사 (24.6%) 순으로 나타났다. 지역별로 분석에서는 매우 높은 유의성 (p<0.001)을 보였고, 사육규모별로 구입경로는 유의성 있는 차이가 없었다 (p>0.05). 항생제 구입빈도는 1회이하/년 (38.6%)가 가장 많았으며, 그 다음은 1회/4~6월 (24.6%), 1~2회/월 (23.7%), 1회/2~3월 (13.2%) 순으로 나타났다. 지역별로는 높은 수준의 유의적인 차이 (p<0.01)로 구입 빈도가 나타났으나, 규모별로는 유의적인 차이가 없었다 (p>0.05). 항생제 대체제에 대한 조사에서는 생균제류 (50.9%)가 가장 많이 차지하였으며, 그 다음으로는 면역제제류 (24.8%)와 백신류 (24.8%)로 나타났다. 지역별 대체제로는 매우 높게 유의적인 차이 (p<0.001)를 보였으나, 규모별로는 유의성있는 차이가 없었다 (p>0.05). 한우농가에서는 앞으로 항생제 대체제로 생균제를 더욱 많이 사용할 것으로 나타나 질병치료나 예방관리에 효율적 활용이 요구된다.

• Bulletin of the Korean Chemical Society
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• 제35권9호
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• pp.2809-2812
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• 2014

The 43-residue defensin-like peptide coprisin, which is isolated from dung bettle, Copris tripartitus, is a potent antimicrobial peptide. In our previous work, we determined the tertiary structure of coprisin and found that alpha helical region of coprisin from residue 19 to residue 30 is important for its antimicrobial activities. Here, we designed cop12mer and cop9mer analogs of coprisin based on the tertiary structure of coprisin. To investigate the relationship between hydrophobicity and antimicrobial activities and develop the potent peptide antibiotics, we designed cop9mer-1 with substitution of $His^2$ with Trp in cop9mer. The results showed that cop9mer-1 has higher toxicities as well as improved antimicrobial activities compared to cop9mer. In order to reduce the toxicity of cop9mer-1, we designed cop9mer-2 and cop9mer-3 with substitution of $Cys^3$ with Lys or Ser. Substitution of $Cys^3$ with these hydrophilic amino acids results in lower cytotoxicities compared to cop9mer-1. Cop9mer-2 with substitution of $Cys^3$ with Lys in Cop9mer-1 showed high antibacterial activities against drug resistant bacteria without cytotoxicity. Antibiotic action of cop9mer-1 analog appears to involve permeabilization of the bacterial cell membrane while cop9mer-2 and cop9mer-3 may have different mechanism of action. These results imply that that optimum balance in hydrophobicity and hydrophilicity in these 9-meric peptides plays key roles in their antimicrobial activities as well as cytotoxicities.

• Journal of Microbiology and Biotechnology
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• 제28권6호
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• pp.1030-1036
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• 2018

Bacillus strains produce various types of antibiotics, and random mutagenesis has traditionally been used to overproduce these natural metabolites. However, this method leads to the accumulation of unwanted mutations in the genome. Here, we rationally designed a single nucleotide substitution in the degU gene to generate a B. subtilis strain displaying increased plipastatin production in a foreign DNA-free manner. The mutant strain (BS1028u) showed improved antifungal activity against Pythium ultimum. Notably, pps operon deletion in BS1028u resulted in complete loss of antifungal activity, suggesting that the antifungal activity strongly depends on the expression of the pps operon. Quantitative real-time PCR and lacZ assays showed that the point mutation resulted in 2-fold increased pps operon expression, which caused the increase in antifungal activity. Likewise, commercial Bacillus strains can be improved to display higher antifungal activity by rationally designed simple modifications of their genome, rendering them more efficient biocontrol agents.

• 한국자기공명학회논문지
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• 제21권3호
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• pp.78-84
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• 2017

Pseudin is a naturally occurring 24 amino-acid-residue antimicrobial peptide derived from the skin of paradoxical frog Pseud's paradoxa. It shows potency against the bacteria and antibiotic-resistant bacteria strain, but has high cytotoxicity against mammalian cell. In our previous study, substitution of $Pro^{11}$ for Gly (Ps-P) increased bacterial cell selectivity but decreased the antibacterial activity of pseudin. In this study, we designed pseudin analogue, Ps-4K-P with increased cationicity up to +7 in Ps-P by substituting Glu14, Gln10, Gln24, and Leu18 with Lys. Ps-4K-P showed improved potent antibacterial activity with high bacterial cell selectivity. We determined the tertiary structure of Ps-4K-P in the presence of DPC micelles by NMR spectroscopy and it has a hinge structure at $Pro^{11}$ followed by three turn helices from $Pro^{11}$ to $Val^{23}$ at the C-terminus. Amphipathicity with increased cationicity as well as helix-hinge-helix structural motif provided by introduction of a Pro at position $Gly^{11}$ are the crucial factors which confer antibacterial activity with bacterial cell selectivity to Ps-4K-P.

• Bulletin of the Korean Chemical Society
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• 제33권9호
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• pp.2883-2889
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• 2012

LL-37 is the only antimicrobial peptide (AMP) of the human cathelicidin family. In addition to potent antimicrobial activity, LL-37 is known to have the potential to inhibit lipolysaccharide (LPS)-induced endotoxic effects. To provide the stability to proteolytic digestion and increase prokaryotic selectivity and/or anti-endotoxic activity of two Lys/Trp-substituted 19-meric antimicrobial peptides (a4-W1 and a4-W2) designed from IG-19 (residues 13-31 of LL-37), we synthesized the diastereomeric peptides (a4-W1-D and a4-W2-D) with D-amino acid substitution at positions 3, 7, 10, 13 and 17 of a4-W1 and a4-W2, respectively and the enantiomeric peptides (a4-W1-E and a4-W2-E) composed D-amino acids. The diastereomeric peptides exhibited the best prokaryotic selectivity and effective protease stability, but no or less anti-endotoxic activity. In contrast, the enantiomeric peptides had not only prokaryotic selectivity and anti-endotoxic activity but also protease stability. Our results suggest that the hydrophobicity and ${\alpha}$-helicity of the peptide is important for anti-endotoxic activity. In particular, the enantiomeric peptides showed potent anti-endotoxic and LPS-neutralizing activities comparable to that of LL-37. Taken together, both a4-W1-E and a4-W2-E holds promise as a template for the development of peptide antibiotics for the treatment of endotoxic shock and sepsis.

• Journal of Animal Science and Technology
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• 제63권3호
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• pp.465-474
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• 2021

It has become important to explore alternative feed ingredients to reduce feed costs, which are burdensome for livestock production. In addition, it is desirable to find efficient and functional alternative ingredients for traditional feed ingredients in pig diets, considering the stress and sensitivity of disease of pig. Rice is produced around the world like corn that is the typical energy source in pig diets. Although the nutritional quality varies depending on the degree of milling, rice, except whole grains (paddy rice), contains more starch than corn and its structure and granule size are easier to digest than corn. In addition, the fact that rice has fewer non-starch polysaccharides (NSP) and anti-nutritional factors (ANFs) is also effective in improving digestibility and various polyphenols in rice can help modulation of immune responses, which can be beneficial to the gastrointestinal environment and health of pig. Many studies have been conducted on rice focusing on things such as degree of milling, substitution rates of corn, granule size, and processing methods. Most results have shown that rice can be partially or completely used to replace corn in pig diets without negatively affecting pig growth and production. While further research should focus on the precise biological mechanisms at play, it was confirmed that the use of rice could reduce the use of antibiotics and pig removal and protect pigs from gastrointestinal diseases including diarrhea. From this point of view, rice can be evaluated as a valuable feed ingredient for swine diets.

• 한국미생물생명공학회:학술대회논문집
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• 한국미생물생명공학회 2002년도 학술발표대회
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• pp.18-25
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• 2002

The pikromycin biosynthetic system in Streptomyces venezuleae is unique for its ability to produce two groups of antibiotics that include the 12-membered ring macrolides methymycin and neomethymycin, and the 14-membered ring macrolides narbomycin and pikromycin. The metabolic pathway also contains two post polyketide-modification enzymes, a glycosyltransferase and P450 hydroxylase that have unusually broad substrate specificities. In order to explore further the substrate flexibility of these enzymes a series of hybrid polyketide synthases were constructed and their metabolic products characterized. The plasmid-based replacement of the multifunctional protein subunits of the pikromycin PKS in S. venezuelae by the corresponding subunits from heterologous modular PKSs resulted in recombinant strains that produce both 12- and 14-membered ring macrolactones with predicted structural alterations. In all cases, novel macrolactones were produced and further modified by the DesVII glycosyltransferase and PikC hydroxylase leading to biologically active macrolide structures. These results demonstrate that hybrid PKSs in S. venezuelae can produce a multiplicity of new macrolactones that are modified further by the highly flexible DesVII glycosyltransferase and PikC hydroxylase tailoring enzymes. This work demonstrates the unique capacity of the S. venezuelae pikromycin pathway to expand the toolbox of combinatorial biosynthesis and to accelerate the creation of novel biologically active natural products. The polyketide backbone of rifamycin B is assembled through successive condensation and ${\beta}$-carbonyl processing of the extender units by the modular rifamycin PKS. The eighth module, in the RifD protein, contains nonfunctional DH domain and functional KR domain, which specify the reduction of the ${\beta}$-carbonyl group resulting in the C-21 bydroxyl of rifamycin B. A four amino acid substitution and one amino acid deletion were introduced in the putative NADPH binding motif in the proposed KR domain encoded by rifD. This strategy of mutation was based on the amino acid sequences of the corresponding motif of the KR domain of module 3 in the RifA protein, which is believed dysfunctional, so as to introduce a minimum alteration and retain the reading frame intact, yet ensure loss of function. The resulting strain produces linear polyketides, from tetraketide to octaketide, which are also produced by a rifD disrupted mutant as a consequence of premature termination of polyketide assembly. Much of the structural diversity within the polyketide superfamily of natural products is due to the ability of PKSs to vary the reduction level of every other alternate carbon atom in the backbone. Thus, the ability to introduce heterologous reductive segments such as ketoreductase (KR), dehydratase (DH), and enoylreductase (ER) into modules that naturally lack these activities would increase the power of the combinatorial biosynthetic toolbox. The dehydratase domain of module 7 of the rifamycin PKS, which is predicted to be nonfunctional in view of the sequence of the apparent active site, was replaced with its functional homolog from module 7 of rapamycin-producing polyketide synthase. The resulting mutant strain behaved like a rifC disrupted mutant, i.e., it accumulated the heptaketide intermediate and its precursors. This result points out a major difficulty we have encountered with all the Amycolatopsis mediterranei strain containing hybrid polyketide synthases: all the engineered strains prepared so far accumulate a plethora of products derived from the polyketide chain assembly intermediates as major products instead of just analogs of rifamycin B or its ansamycin precursors.