KR20230046626A - 항염증 활성을 나타내는 알칼리성 단백질 분해효소를 포함하는 조성물 - Google Patents
항염증 활성을 나타내는 알칼리성 단백질 분해효소를 포함하는 조성물 Download PDFInfo
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Abstract
본 발명은 항염증 활성을 나타내는 알칼리성 단백질 분해효소 조성물에 관한 것으로서, 바실러스 클라우지(Bacillus clausii) I-52 균주(수탁번호 : KCTC 10277BP)에서 유래된 서열번호 1의 DNA를 기준으로 생산된 서열번호 2 또는 서열번호 3의 알칼리성 단백질 분해효소를 유효성분으로 포함한다.
상기와 같은 본 발명에 따르면, 바실러스 클라우지(Bacillus clausii) I-52 균주(수탁번호 : KCTC 10277BP)에서 생산된 알칼리성 단백질 분해효소를 포함하는 조성물은, 염증성 질환의 치료, 개선 또는 예방할 수 있는 효과가 있으며, 특히 pH 7 이상의 알칼리성 범위에서 최대 항염증 활성을 나타낸다.
상기와 같은 본 발명에 따르면, 바실러스 클라우지(Bacillus clausii) I-52 균주(수탁번호 : KCTC 10277BP)에서 생산된 알칼리성 단백질 분해효소를 포함하는 조성물은, 염증성 질환의 치료, 개선 또는 예방할 수 있는 효과가 있으며, 특히 pH 7 이상의 알칼리성 범위에서 최대 항염증 활성을 나타낸다.
Description
본 발명은 항염증 활성을 나타내는 알칼리성 단백질 분해효소(alkaline protease, AP)를 포함하는 조성물에 관한 것으로, 더욱 상세하게는 바실러스 클라우지(Bacillus clausii) I-52 균주(수탁번호 : KCTC 10277BP)에서 생산된 알칼리성 단백질 분해효소의 항염증 활성 효과를 확인하고, 알칼리성 단백질 분해효소를 유효성분으로 포함하는 조성물에 관한 것이다.
체내 염증반응은 다양한 면역세포들의 유도성 활성으로 매개되는 일련의 신호전달 경로에 의하여 조직 및 기관손상을 유발하고 암을 포함한 인체질환의 근본적인 원인으로 작용한다. 이와 같은 염증반응이 시작될 때 가장 우선적으로 대식세포(macrophage)가 활성화되며, 이때 박테리아를 포함한 감염균들의 구성성분(예: lipopolysaccharide, LPS)과 TNF-alpha 및 Interleukins를 포함한 다양한 Cytokine 들의 분비로 염증 반응이 유도되거나 촉진된다.
이와 같은 대식세포의 활성화 정도는 iNOS(inducible nitric oxide synthase, NOS2)와 Cyclooxygenase-2(COX-2)와 같은 염증반응 매개 효소계들의 유도발현과 Nitric Oxide(NO)와 Prostaglandin E2(PGE2) 생성물질들의 농도를 측정함으로써 비교 평가할 수 있다. 특히, 고농도의 NO와 PGE2의 유도생성은 급성뿐 아니라 만성 염증반응 기전에도 작용하여, 정상조직과 기관 손상 및 세포사(necrosis, apoptosis) 유발의 원인물질로 제시되고 있다. 그러므로 iNOS와 COX-2와 같은 유도발현을 억제하고, NO와 PGE2의 생성 정도를 조절할 수 있는 물질들은 대식세포의 유도 및 활성화를 조절할 수 있는 염증반응 조절 또는 항염증 활성 물질로 평가될 수 있다.
이에 본 발명은 바실러스 클라우지(Bacillus clausii) I-52 균주에서 유래된 서열번호 1의 DNA를 기준으로 생산된 서열번호 2 또는 서열번호 3의 알칼리성 단백질 분해효소를 포함하는 조성물을 제공하고자 한다.
본 발명의 목적은, 바실러스 클라우지(Bacillus clausii) I-52 균주(수탁번호 : KCTC 10277BP)에서 유래된 서열번호 1의 DNA를 기준으로 생산된 서열번호 2 또는 서열번호 3의 알칼리성 단백질 분해효소를 사용하여 염증성 질환을 치료, 개선 또는 예방할 수 있는 조성물을 제공하는 것이다.
상기 목적을 달성하기 위하여, 본 발명은 바실러스 클라우지(Bacillus clausii) I-52 균주(수탁번호 : KCTC 10277BP)에서 유래된 서열번호 1의 DNA를 기준으로 생산된 서열번호 2 또는 서열번호 3의 알칼리성 단백질 분해효소(alkaline protease)를 포함하고, 사이토카인과 섬유화 및 염증세포 이동에 관여하는 단백질의 발현량을 감소시킬 수 있다.
바람직하게, 상기 조성물은 알칼리성 단백질 분해효소를 1 내지 500 ug/ml 포함할 수 있고, 더욱 바람직하게는 10 내지 100 ug/ml을 포함할 수 있다.
바람직하게, 상기 상기 사이토카인은 IL-6, IL-8, TNF-γ 및 TNF-α중 어느 하나 이상이고, 상기 섬유화 및 염증세포 이동에 관여하는 단백질은 NF-κB, MMP2 및 MMP9 중 어느 하나 이상일 수 있다.
바람직하게, 상기 조성물을 유효성분으로 포함하는 건강기능식품을 제공할 수 있다.
상기와 같은 본 발명에 따르면, 바실러스 클라우지(Bacillus clausii) I-52 균주(수탁번호 : KCTC 10277BP)에서 유래된 서열번호 1의 DNA를 기준으로 생산된 서열번호 2 또는 서열번호 3의 알칼리성 단백질 분해효소는 염증성 면역 반응을 개선 또는 치료에 탁월한 효과가 있고, 염증성 면역 질환을 예방, 개선 및 치료하는 효과가 있으며, 특히 pH 7 이상의 알칼리성 범위에서 최대 항염증 활성을 나타낸다.
도 1은 IL-1β 자극을 받은 마우스 폐 상피세포(MLE12)에서 알칼리성 단백질 분해효소의 흡광도 및 세포독성(cytotoxicity, [%])을 MTT 분석법을 통해 나타낸 그래프이다.
도 2는 본 발명에 따른 알칼리성 단백질 분해효소에 대해서 RNA 수준에서 항염증 효과를 확인하기 위해 사이토카인과 섬유화 및 염증 반응에 관여하는 단백질의 발현량을 나타낸 그래프이다.
도 2는 본 발명에 따른 알칼리성 단백질 분해효소에 대해서 RNA 수준에서 항염증 효과를 확인하기 위해 사이토카인과 섬유화 및 염증 반응에 관여하는 단백질의 발현량을 나타낸 그래프이다.
이하, 본 발명을 상세히 설명한다.
본 발명은 바실러스 클라우지(Bacillus clausii) I-52 균주(수탁번호 : KCTC 10277BP)에서 생산된 알칼리성 단백질 분해효소를 포함하는 조성물을 제공한다.
상기 바실러스 클라우지 I-52 균주에서 유래된 서열번호 1의 DNA를 기준으로 생산된 서열번호 2 또는 서열번호 3의 단백질 분해효소는 특허등록번호 제10-07506559호에 개시된 단백질 분해 효소로 상기 바실러스 클라우지 I-52 균주로부터 염색체 DNA를 분리한 다음, 분리된 DNA를 주형으로, 중합효소 연쇄반응을 수행하여 얻은 단백질 분해효소(펄자임, Pearlzyme)이다. 상기 DNA는 서열번호 1의 DNA와 같은 염기서열을 가지며, 상기 단백질 분해효소(펄자임, Pearlzyme)는 서열번호 2 또는 3의 단백질 서열을 가진다.
상기 조성물은 바실러스 클라우지 I-52 균주에서 생산된 알칼리성 단백질 분해효소를 1 내지 100 ug/ml 포함할 수 있다.
알칼리성 단백질 분해효소를 유효성분으로 포함하는 조성물 및 상기 조성물을 유효성분으로 포함하는 건강기능식품은 염증성 면역 질환을 예방, 개선 및 치료할 수 있고, 상기 염증성 질환은 염증성 피부질환, 패혈증, 크론병, 궤양성 대장염, 복막염, 골수염, 봉소염, 뇌막염, 뇌염, 췌장염,외상 유발 쇼크, 기관지 천식, 알레르기성 비염, 낭포성 섬유증, 뇌졸중, 급성 기관지염, 만성 기관지염, 골관절염, 통풍, 척추관절병증, 강직성 척추염, 장질환 척추염, 연소자성 관절병증, 연소자성 강직성 척추염, 반응성 관절병증, 감염성 관절염, 전신성 홍반성 루푸스, 재귀열, 건선, 후-감염성 관절염, 임균성 관절염, 결핵성 관절염, 바이러스성 관절염, 진균성 관절염, 매독성 관절염, 류마티스성 다발성근육통, 관절 세포 동맥염, 칼슘 결정 침착 관절병증, 비-관절 류마티즘, 점액낭염, 건초염, 및 혈색소증 중에서 선택된 어느 하나일 수 있다.
상기와 같이 본 발명은 바실러스 클라우지(Bacillus clausii) I-52 균주에서 생산된 알칼리성 단백질 분해효소의 염증반응 억제 또는 항염증 활성에 관한 것으로서, 염증반응을 유도한 모델을 적용하여 하기의 실시예들을 통해 그 결과를 확인하였다.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 예시하기 위한 것으로서, 본 발명의 범위가 이들 실시예에 의해 제한되는 것으로 해석되지는 않는 것은 당업계에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.
실시예 1. MTT 분석법을 통한 알칼리성 단백질 분해효소(AP)의 세포독성 확인
MTT 분석법은 세포 대사 활성을 평가하는 비색법(colorimetric assay)으로, 단백질 분해효소의 세포독성(cytotoxicity)을 MTT 분석법을 통해 확인하였다.
96 well plate(제조사 : Thermo Fisher scientific, USA)에 마우스 폐 상피세포(MLE12, American type culture collection, USA)를 5×104 cells/100 ul로 세포 배양판에 부착시켰다. 그 후, 24시간 절식시킨 뒤, 알칼리성 단백질 분해효소 1, 10, 25, 50, 75 및 100 ug/ml에 대해 처리하였다. 노출시간은 각각 0.5, 1. 2. 6 및 24시간으로 진행하였다. 그리고 IL-1β(cell signaling technology, USA) 10 ng/ml로 1시간 동안 자극 후 MTT labeling reagent로서, 3-(4,5-디메틸-2-티아졸일)-2,5디페닐-2H-테트라졸륨 브로마이드(제조사 : Sigma Aldrich, USA)를 처리하였다. 4시간 뒤 solubilization solution으로 처리 후, 12시간 이상 37℃ incubator에서 보관한 뒤, 550 nm에서 흡광도를 측정하고, 650 nm로 보정하였다.
MTT 분석 결과, 대조군(con)과 비교하였을 때, IL-1β에서 550 nm 흡광도가 감소하는 경향을 보이고, IL-1β와 비교하여, AP 1, 10, 25 및 50 ug/ml에서 대조군(con)보다는 감소하고, IL-1β보다 증가하는 경향을 확인하였다.
Cytotoxicity [%]의 경우, 대조군과 비교한 실험군의 흡광도를 상대적 백분율로 계산한 것이고, 그 방정식은 아래와 같다.
광학 농도(optical density, OD) 값은 아래 [표 1]에, 세포독성(%)은 [표 2]에 나타내었다.
실시예 2. 알칼리성 단백질 분해효소의 항염증 효과 확인
실시예 1.에서 IL-1β의 자극에도 세포독성(cytotoxicity [%])이 감소하는 것으로 나타난 알칼리성 단백질 분해효소(alkaline protease, AP) 1, 10, 25 및 50 ug/ml에 대해서, RNA 수준에서의 항염증 효과를 확인하기 위해 실시간 중합효소연쇄반응(real-time PCR)을 수행하였다.
먼저, 6 well plate(제조사 : Thermo Fisher Scientific, USA)에 마우스 폐 상피세포(MLE12)를 3 × 105 cells/ml로 세포 배양판에 부착시켰다. 이후 24시간 동안 절식시킨 뒤, 알칼리성 단백질 분해효소 1, 10, 25 및 50 ug/ml에 대해 1시간 동안 처리하였다. 이후 IL-1β 10 ng/ml에 대해 1시간 동안 자극하고, 세포 회수를 진행하였다. RNA isolation kit(제조사 : QIAGEN, Germany)를 이용하여 회수한 세포에서 RNA 추출 후 cDNA synthesis kit (제조사 : Agilent, USA)를 이용하여 cDNA를 합성하였다. 이후 사이토카인 4 종류(IL-6, IL-8, IFN-γ 및 TNF-α)와 섬유화(fibrosis) 및 염증 반응에 관여하는 인자 3 종류(NF-κB, MMP2 및 MMP9)에 대해 실시간 중합효소연쇄반응을 수행하였다. IL-6와 NF-κB 프라이머(primer)는 quantitect primer assays (제조사 : Qiagen, Germany)를 구매하여 사용하였고, 나머지 primer에 대한 정보는 하기 [표 3]과 같다. 각각의 RNA 발현량은 GAPDH를 이용해 보정하였다.
| Gene | Primer Sequence | |
| IL-8 | Forward | 5’-CTA GGC ATC TTC GTC CGT CC-3’ |
| Reverse | 5’-TTG GGC CAA CAG TAG CCT TC-3’ | |
| IFN-γ | Forward | 5’-ATC CTG GAG GAA CTG GCA AAA-3’ |
| Reverse | 5’-TTC AAG ACT TCA AAG AGT CTG AGG T-3’ | |
| TNF-α | Forward | 5’-CCA CGC TCT TCT GTC TAC TGA-3’ |
| Reverse | 5’-GCT ACA GGC TTG TCA CTC G-3’ | |
| MMP2 | Forward | 5’-GAT AAC CTG GAT GCC CTG GTG-3’ |
| Reverse | 5’-CTT CAC GCT CTT GAG ACT TTG GTT-3’ | |
| MMP9 | Forward | 5’-GCC CTG GAA CTC ACA CGA CA-3’ |
| Reverse | 5’-TTG GAA ACT CAC ACG CCA GAA G-3’ | |
| GAPDH | Forward | 5’-AGG TCG GTG TGA ACG GAT TTG-3’ |
| Reverse | 5’-TGT AGA CCA TGT AGT TGA GGT C-3’ | |
도 2는 실시간 중합효소연쇄반응 결과이다. 대조군(CON)과 비교하여 IL-1β에서 사이토카인(IL-6, IL-8, IFN-γ 및 TNF-α)과 섬유화 및 염증세포 이동에 관여하는 NF-κB, MMP2 및 MMP9에 유의미하게 증가하는 경향을 보이고, IL-1β와 비교하여 알칼리성 단백질 분해효소 25 및 50 ug/ml에서 유의미하게 감소하는 경향을 보인다.
실시예 3. 실시간 중합효소연쇄반응(real-time PCR) 수행
실시예 2.에서 사이토카인 4 종류(IL-6, IL-8, IFN-γ 및 TNF-α)와 섬유화 및 염증 반응에 관여하는 인자 3 종류(NF-κB, MMP2 및 MMP9)에서 감소효과를 보이는 알칼리성 단백질 분해효소 25 및 50 ug/ml에서 그 효과를 치료제 또는 억제제와 비교하기 위해 RNA 수준에서 실시간 중합효소연쇄반응을 수행하였다.
GM6001 (제조사 : Tocris, UK)은 몇몇 MMP 억제제로 보고되고, 세포에서의 TNF-α 방출 및 처리 과정에서 길항제로 작용하는 것으로 알려져 있다.
6 well plate에 마우스 폐 상피세포(MLE12)를 3 × 105 cells/ml로 세포 배양판에 부착시켰다. 이후 24시간 동안 절식시킨 뒤, 알칼리성 단백질 분해효소 25 및 50 ug/ml와 GM6001 0.1m을 1시간 동안 처리하였다. 그리고 IL-1β 10 ng/ml에 대해 1시간 동안 자극하고, 세포회수를 진행하였다. RNA isolation kit를 이용하여 cDNA를 합성하였다. 이후 사이토카인 4 종류(IL-6, IL-8, IFN-γ 및 TNF-α)와 섬유화 및 염증 반응에 관여하는 인자 3 종류(NF-κB, MMP2 및 MMP9)에 대해 실시간 중합효소연쇄반응을 수행하였다.
실시간 중합효소연쇄반응 수행 결과, 대조군(CON)과 비교하여 IL-1β에서 염증성 사이토카인(IL-6, IL-8, IFN-γ 및 TNF-α)과 섬유화 및 염증세포 이동에 관여하는 NF-κB, MMP2 및 MMP9에 대해 유의미하게 증가하는 경향을 보이고, IL-1β과 비교하여 GM6001 그룹과 AP 25 및 50 ug/ml에서 유의미하게 감소하는 경향을 보인다. 그리고, GM6001과 비교하여 알칼리성 단백질 분해효소 25 및 50 ug/ml의 치료효과가 비슷한 경향성을 보인다. 특히, 알칼리성 단백질 분해효소 50 ug/ml의 치료효과가 GM6001과 비슷한 결과를 보인다.
이상, 본 발명내용의 특정한 부분을 상세히 기술하였는바, 당업계의 통상의 지식을 가진 자에게 있어서, 이러한 구체적인 기술은 단지 바람직한 실시양태일 뿐이며, 이에 의해 본 발명의 범위가 제한되는 것이 아닌 점은 명백할 것이다. 따라서 본 발명의 실질적인 범위는 첨부된 청구항들과 그것들의 등가물에 의해 정의된다고 할 것이다.
<110> JANG, jeongsun
JEONG, suyeon
<120> Enzyme composition showing inhibitory or regulatory activity
<130> P19-E349
<160> 3
<170> KoPatentIn 3.0
<210> 1
<211> 2280
<212> DNA
<213> Unknown
<220>
<223> artificial sequence
<400> 1
aacgttgaca ttcggcacac tccttttcat ttatatcgta accgaagaac gttcaaaaaa 60
ccaaatcatc aagccgccat tttcacttcg ccggcacatt gagagaataa tggacaaatc 120
cggtatcctc ttcatagccg ttttgctcat acaagcttct tgccttccgg ttgtggtgct 180
cagtctgaag cgttaaacat tttgccccgt tttcccctgc ataatccttt gcggcagaaa 240
gcagccggcc gccggctccc tttgtacgcg catgaggaac gacaaataag tcatttaata 300
tgtagatcct tttcattgac acagaagaaa acgttggata gagctgggta aagcctatga 360
attctccatt ttcttctgct atcaaaataa cagactcgtg attttccaaa cgagctttca 420
aaaaagcctc cgccccttgc aaatcggatg cctgtctata aaattcacga tattggttaa 480
acaacggcgc aatggcggcc gcatctgatg tctttgcttg gcgaatgttc atcttatttc 540
ttcctccctc tcaataattt ttttattcta tcccttttct gtaaagttta tttttcagaa 600
tacttttatc atcatgcttt gaaaaaatat cacgataata tccattgttc tcacggaagc 660
atatacaggt catttgaacg aattttttcg acaggaattt gcagggactc aggagcattt 720
aacctaaaaa agcatgacat ttcagcataa tgaacattta ctcatgtcta ttttcgttct 780
tttctgtatg aaaatagtta tttcgagtct ctacggaaat agcgagagat gatataccta 840
aatagagata aaatcatctc aaaaaaatgg gtctactaaa atattattcc atctattaca 900
ataaattcac agaatagtct tttaagtaag tctactctga atttttttaa aaggagaggg 960
taaagagtga gaagcaaaaa attgtggatc agcttgttgt ttgcgttaac gttaatcttt 1020
acgatggcgt tcagcaacac gtctgcgcag gctgccggaa aaagcagtac agaaaagaaa 1080
tacattgtcg gatttaagca gacaatgagt gccatgagtt ccgccaagaa aaaggatgtt 1140
atttctgaaa aaggcggaaa ggttcaaaag caatttaagt atgttaacgc ggccgcagca 1200
acattggatg aaaaagctgt aaaagaattg gaaaaagatc cgagcgttgc atatgtggaa 1260
gaagatcata ttgcacatga atatgcgcaa tctgttcctt atggcatttc tcaaattaaa 1320
gcgccggctc ttcactctca aggctacaca ggctctaacg taaaagtagc tgttattgac 1380
agcggaattg actcttctca tcctgactta aacgtcagag gcggagcaag tttcgtacct 1440
tctgaaacaa acccatacca ggacggcagt tctcacggta cgcatgtagc cggtacgatt 1500
gccgctctta ataactcaat cggtgttctg ggcgtagcgc caagcgcatc attatatgca 1560
gtaaaagtgc ttgattcaac aggaagcggc caatatagct ggattattaa cggcattgag 1620
tgggccattt ccaacaatat ggatgttatc aacatgagcc ttggcggacc tactggttct 1680
acagcgctga aaacagtcgt tgacaaagcc gtttccagcg gtatcgtcgt tgctgccgct 1740
gccggaaacg aaggttcgtc cggaagctca agcacagtcg gctaccctgc aaaatatcct 1800
tctactattg cggtaggtgc ggtaaacagc agcaaccaaa gagcttcatt ctcaagcgca 1860
ggttctgagc ttgatgtgat ggctcctggc gtatccatcc aaagcacact tcctggaggc 1920
acttacggtg cttacaacgg cacgtccatg gcgactcctc acgttgccgg agcagcagcg 1980
ttaattcttt ctaagcaccc gacttggaca aacgcgcaag tccgtgatcg tttagaaagc 2040
actgcaacat atcttggaaa ctctttctac tatggaaaag ggttaatcaa cgtacaagca 2100
gctgcacaat aatagtaaaa agaagcaggt tcctccatac ctgcttcttt ttatttgtca 2160
gcatcctgat gttccggcgc attctcttct ttttccgcat gttgaatccg ttccatgatc 2220
gacggatggc tgcctctgaa aatcttcaca agcaccggag gatcaacctg gctcagcccc 2280
2280
<210> 2
<211> 381
<212> PRT
<213> Unknown
<220>
<223> Bacillus clausii
<400> 2
Met Arg Ser Lys Lys Leu Trp Ile Ser Leu Leu Phe Ala Leu Thr Leu
1 5 10 15
Ile Phe Thr Met Ala Leu Ser Asn Met Ser Ala Gln Ala Ala Gly Lys
20 25 30
Ser Ser Thr Glu Lys Lys Tyr Ile Val Gly Phe Lys Gln Thr Met Ser
35 40 45
Ala Met Ser Ser Ala Lys Lys Lys Asp Val Ile Ser Glu Lys Gly Gly
50 55 60
Lys Val Gln Lys Gln Phe Lys Tyr Val Asn Ala Ala Ala Ala Thr Leu
65 70 75 80
Asp Glu Lys Ala Val Lys Glu Leu Lys Lys Asp Pro Ser Val Ala Tyr
85 90 95
Val Glu Glu Asp His Ile Ala His Glu Tyr Ala Gln Ser Val Pro Tyr
100 105 110
Gly Ile Ser Gln Ile Lys Ala Pro Ala Leu His Ser Gln Gly Tyr Thr
115 120 125
Gly Ser Asn Val Lys Val Ala Val Ile Asp Ser Gly Ile Asp Ser Ser
130 135 140
His Pro Asp Leu Asn Val Arg Gly Gly Ala Ser Phe Val Pro Ser Glu
145 150 155 160
Thr Asn Pro Tyr Gln Asp Gly Ser Ser His Gly Thr His Val Ala Gly
165 170 175
Thr Ile Ala Ala Leu Asn Asn Ser Ile Gly Val Leu Gly Val Ala Pro
180 185 190
Ser Ala Ser Leu Tyr Ala Val Lys Val Leu Asp Ser Thr Gly Ser Gly
195 200 205
Gln Tyr Ser Trp Ile Ile Asn Gly Ile Glu Trp Ala Ile Ser Asn Asn
210 215 220
Met Asp Val Ile Asn Met Ser Leu Gly Gly Pro Thr Gly Ser Thr Ala
225 230 235 240
Leu Lys Thr Val Val Asp Lys Ala Val Ser Ser Gly Ile Val Val Ala
245 250 255
Ala Ala Ala Gly Asn Glu Gly Ser Ser Gly Ser Thr Ser Thr Val Gly
260 265 270
Tyr Pro Ala Lys Tyr Pro Ser Thr Ile Ala Val Gly Ala Val Asn Ser
275 280 285
Ser Asn Gln Arg Ala Ser Phe Ser Ser Ala Gly Ser Glu Leu Asp Val
290 295 300
Met Ala Pro Gly Val Ser Ile Gln Ser Thr Leu Pro Gly Gly Thr Tyr
305 310 315 320
Gly Ala Tyr Asn Gly Thr Ser Met Ala Thr Pro His Val Ala Gly Ala
325 330 335
Ala Ala Leu Ile Leu Ser Lys His Pro Thr Trp Thr Asn Ala Gln Val
340 345 350
Arg Asp Arg Leu Glu Ser Thr Ala Thr Tyr Leu Gly Asn Ser Phe Tyr
355 360 365
Tyr Gly Lys Gly Leu Ile Asn Val Gln Ala Ala Ala Gln
370 375 380
<210> 3
<211> 275
<212> PRT
<213> Unknown
<220>
<223> Bacillus clausii
<400> 3
Ala Gln Ser Val Pro Tyr Gly Ile Ser Gln Ile Lys Ala Pro Ala Leu
1 5 10 15
His Ser Gln Gly Tyr Thr Gly Ser Asn Val Lys Val Ala Val Ile Asp
20 25 30
Ser Gly Ile Asp Ser Ser His Pro Asp Leu Asn Val Arg Gly Gly Ala
35 40 45
Ser Phe Val Pro Ser Glu Thr Asn Pro Tyr Gln Asp Gly Ser Ser His
50 55 60
Gly Thr His Val Ala Gly Thr Ile Ala Ala Leu Asn Asn Ser Ile Gly
65 70 75 80
Val Leu Gly Val Ala Pro Ser Ala Ser Leu Tyr Ala Val Lys Val Leu
85 90 95
Asp Ser Thr Gly Ser Gly Gln Tyr Ser Trp Ile Ile Asn Gly Ile Glu
100 105 110
Trp Ala Ile Ser Asn Asn Met Asp Val Ile Asn Met Ser Leu Gly Gly
115 120 125
Pro Thr Gly Ser Thr Ala Leu Lys Thr Val Val Asp Lys Ala Val Ser
130 135 140
Ser Gly Ile Val Val Ala Ala Ala Ala Gly Asn Glu Gly Ser Ser Gly
145 150 155 160
Ser Thr Ser Thr Val Gly Tyr Pro Ala Lys Tyr Pro Ser Thr Ile Ala
165 170 175
Val Gly Ala Val Asn Ser Ser Asn Gln Arg Ala Ser Phe Ser Ser Ala
180 185 190
Gly Ser Glu Leu Asp Val Met Ala Pro Gly Val Ser Ile Gln Ser Thr
195 200 205
Leu Pro Gly Gly Thr Tyr Gly Ala Tyr Asn Gly Thr Ser Met Ala Thr
210 215 220
Pro His Val Ala Gly Ala Ala Ala Leu Ile Leu Ser Lys His Pro Thr
225 230 235 240
Trp Thr Asn Ala Gln Val Arg Asp Arg Leu Glu Ser Thr Ala Thr Tyr
245 250 255
Leu Gly Asn Ser Phe Tyr Tyr Gly Lys Gly Leu Ile Asn Val Gln Ala
260 265 270
Ala Ala Gln
275
Claims (4)
- 바실러스 클라우지(Bacillus clausii) I-52 균주(수탁번호 : KCTC 10277BP)에서 유래된 서열번호 1의 DNA를 기준으로 생산된 서열번호 2 또는 서열번호 3의 알칼리성 단백질 분해효소(alkaline protease)를 포함하고,
사이토카인과 섬유화 및 염증세포 이동에 관여하는 단백질의 발현량을 감소시키는 것을 특징으로 하는 알칼리성 단백질 분해효소를 포함하는 조성물. - 제1항에 있어서,
상기 조성물은 알칼리성 단백질 분해효소를 1 내지 500 ug/ml 포함하는 것을 특징으로 하는 알칼리성 단백질 분해효소를 포함하는 조성물. - 제1항에 있어서,
상기 사이토카인은 IL-6, IL-8, TNF-γ 및 TNF-α중 어느 하나 이상이고, 상기 섬유화 및 염증세포 이동에 관여하는 단백질은 NF-κB, MMP2 및 MMP9 중 어느 하나 이상인 것을 특징으로 하는 알칼리성 단백질 분해효소를 포함하는 조성물. - 제1항에 있어서,
상기 조성물을 유효성분으로 포함하는 건강기능식품.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100750659B1 (ko) | 2005-02-18 | 2007-08-20 | 인하대학교 산학협력단 | 계면활성제 및 산화제에 매우 안정한 호염, 호알카리성 단백질 분해효소 및 이를 암호화하는 유전자 |
| KR102260512B1 (ko) | 2019-10-15 | 2021-06-04 | 장정순 | 염증반응 억제 또는 조절 활성을 나타내는 효소조성물 |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100750659B1 (ko) | 2005-02-18 | 2007-08-20 | 인하대학교 산학협력단 | 계면활성제 및 산화제에 매우 안정한 호염, 호알카리성 단백질 분해효소 및 이를 암호화하는 유전자 |
| KR102260512B1 (ko) | 2019-10-15 | 2021-06-04 | 장정순 | 염증반응 억제 또는 조절 활성을 나타내는 효소조성물 |
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