Discovery of Novel Bioactive Compounds from Marine Microorganisms

신희재 한국공업화학회 2019 한국공업화학회 연구논문 초록집 Vol.2019 No.0

Approximately 30,000 structurally diverse natural products with a vast array of bioactivities have been discovered from marine organisms including microbes, algae and invertebrates. Especially, the study of marine bacteria and their potential role in the production of bioactive metabolites is a rapidly growing field, due to the fact that a number of metabolites obtained from marine macroalgae and invertebrates such as sponges may be produced by associated marine microorganisms. Thus, marine microorganisms have attracted considerable attention due to the structural diversities and unique biological activities of their secondary metabolites. This presentation will highlight the importance of marine microorganisms in the drug discovery from marine natural products. The isolation, structure determination, and bioactivities of novel compounds from marine microorganisms will be presented.

해양미생물 추출물의 동종세포반응 (Allogeneic Mixed Lymphocyte Culture) 억제효능 검색

손병화,윤금자,오근희,이동섭,최홍대,강정숙 한국생약학회 2011 생약학회지 Vol.42 No.4

In order to screen new allogeneic mixed lymphocyte culture (allo-MLR) inhibitor which is expected to be immunomodulating drug lead, we have investigated allo-MLR inhibitory activity on the marine-derived symbiotic microorganisms (1,895 strains) from the marine algae. The potent inhibitory activities (over 45% inhibition of proliferation at 10 and 2 µg/ml)without cytotoxicity were observed in the extracts of 46 strains. While, the significant stimulating activities (over 100% proliferation at 10 and 2 µg/ml) without cytotoxicity were observed in the extracts of 5 strains. In the second assay using 46 bioactive strains, 14 strains exhibited again significant allo-MLR inhibitory activity. Finally, 11 strains among the 14 strains inhibited proliferation and IFN-γ production of CD4+ T cells during the stimulation with specific antigen in the third assay. On the basis of above results, the marine algae is nice source for isolation of immunomodulating microorganism, and the marine algae-associated microorganism is also nice target for development of the new immunomodulating drug lead.

세라믹 다공체 표면에 발생하는 해양 생물 오손 억제에 관한 연구

강지민,강승구,김유택,Kang, Jimin,Kang, Seunggu,Kim, YooTack 한국결정성장학회 2015 한국결정성장학회지 Vol.25 No.5

최근 세라믹 다공체를 이용하여 적조 생물을 여과, 제거하려는 연구가 시도되고 있다. 하지만 해양 환경에서 1개월 이상이 경과하면 다공체 표면에 해양 생물 오손(biofouling)이 발생하여 기능이 저하되는 문제가 나타난다. 본 논문에서는 세라믹 다공체의 특성 변화 또는 표면 개질을 통하여 해양 생물 오손을 억제하는 방법에 대하여 연구하였다. 6 종류의 세라믹 다공체를 시험한 결과, 기공율과 흡수율이 낮을수록 생물 오손량이 낮게 나타났다. 또한 다공체 표면에 실리카 입자를 결합시켜 표면 거칠기를 증가시키면, 따개비 등의 대형 해양 생물로 인한 오손량을 감소시킬 수 있었다. 한편 세라믹 다공체 표면에 유리분말을 융착 코팅시키면 오히려 생물 오손량이 증가하였는데, 이는 유리에서 용출되어 나오는 무기질 성분 이온들이 미생물의 생육을 촉진했기 때문이다. 본 연구로부터 세라믹 다공체의 물리적 성질 및 표면 거칠기를 제어하면 위험 물질을 사용하지 않고도 친환경적으로 해양 생물 오손량을 줄일 수 있음을 확인하였으며, 따라서 본 결과를 향후 해양 구조물 등에 적용할 수 있을 것으로 기대된다. Recently, removing methods of red tide has been attempted by filtering the organisms using the ceramic porous bodies. However, the marine biofouling could be developed on the surfaces of porous ceramic body after use for more than one month, and it might decrease the function of the specimen. In this paper, a method of inhibiting marine biofouling by changing the physical properties or surface-modification of ceramic porous body was studied. After experiment with six different ceramic porous bodies, it was found that the specimen of lower porosity and water absorption showed the least amount of biofouling. In addition, by increasing the surface roughness with silica particles bonded to the surface of specimen, the amount of biofouling caused by large marine life such as barnacle and mussel could be decreased. On the other hand, when the surface of specimen was coated and fused by glass powder, the amount of biofouling was rather increased. This might be due to eluted inorganic ions from the glass which can promote the growth of the microorganism. In conclusion, the environmental-friendly methods to reduce the amount of marine biofouling, such as controlling the physical properties and the surface roughness of the porous ceramics, can be possible without the use of dangerous substances. So it is expected for the results obtained to be applicable to a marine structure.

해양 미생물을 활용한 생명과학 및 생명공학 기술 개발

윤용준(Yongjoon Yoon),윤보현(Bohyun Yun),황성민(Bohyun Yun),문기환(Ki Hwan Moon) 한국생명과학회 2023 생명과학회지 Vol.33 No.7

바다는 지구 표면의 70% 이상을 차지하고 있으며, 그 자체가 대부분 탐사되지 않은 미지와 기회의 공간으로 제시되고 있다. 특히, 우리나라는 삼면이 바다로 둘러싸인 반도로 해양 연구의 중요성이 강조되고 있다. 매우 복잡하고 다양한 환경을 가지고 있는 해양은 막대한 생물학적 다양성을 보이고 있으며 미생물학적 측면에서도 해양 환경은 다양하고 극단적인 온도, 압력, 일사량, 염분, pH 등을 가지고 있어 생태학적으로 특이한 서식처를 제공한다. 이로 인해 육상과는 달리 계통분류학적으로 매우 다르며, 다양한 미생물들이 서식하나 그 다양성, 분리, 배양 그리고 이들이 생산해 내는 2차 대사산물 등에 대한 연구는 아직도 미진한 상황이다. 1990년대까지도 거의 연구되지 않던 해양 환경 자생 미생물의 생리활성물질에 대한 연구는 2000년대 들어 해양 방선균이 생산해 내는 천연물에 대한 연구가 가속화 되기 시작했다. 이후, 박테리아, 고세균, 조류 등을 활용한 항균제, 항암제, 항산화제, 항염증제 등과 같은 의약품 개발 분야 뿐만 아니라 및 바이오 플라스틱 생산, 바이오 연료 생산, 이산화탄소 포집, 생균제 발굴 및 개발 등의 다양한 산업분야에서 해양 미생물을 활용한 연구가 가속화 되고 있는 실정이다. 본 총설에서는 해양미생물을 활용한 생명과학 및 생명공학 기술 분야의 연구 성과 및 최신 동향을 소개하고자 한다. 이를 통해 독자들이 의약소재 개발 외 제반 천연물 관련 분야의 기반 및 응용 연구의 중요성을 인식하고 미래 해양 유래 소재를 이용한 바이오 연구 개발의 최적화 및 실용화 연구에 적극 도움이 되길 기대한다. The ocean accounts for over 70% of the Earth’s surface and is a space of largely unexplored unknowns and opportunities. Korea is a peninsula surrounded by the sea on three sides, emphasizing the importance of marine research. The ocean has an extremely complex environment with immense biological diversity. In terms of microbiology, the marine environment has varying factors like extreme temperature, pressure, solar radiation, salt concentration, and pH, providing ecologically unique habitats. Due to this variety, marine organisms have very different phylogenetic classifications compared with terrestrial organisms. Although various microorganisms inhabit the ocean, studies on the diversity, isolation, and cultivation of marine microorganisms and the secondary metabolites they produce are still insufficient. Research on bioactive substances from marine microorganisms, which were rarely studied until the 1990s, has accelerated in terms of natural products from marine Actinomycetes since the 2000s. Since then, industries for bioplastic and biofuel production, carbon dioxide capture, probiotics, and pharmaceutical discovery and development of antibacterial, anticancer, antioxidant, and anti-inflammatory drugs using bacteria, archaea, and algae have significantly grown. In this review, we introduce current research findings and the latest trends in life science and biotechnology using marine microorganisms. Through this article, we hope to create consumer awareness of the importance of basic and applied research in various natural product-related discovery fields other than conventional pharmaceutical drug discovery. The article aims to suggest pathways that may boost research on the optimization and application of future marine-derived materials.

Recent progresses in marine microbial-derived antiviral natural products

Yun‑Fei Teng,Li Xu,Mei‑Yan Wei,Chang‑Yun Wang,Yu‑Cheng Gu,Chang‑Lun Shao 대한약학회 2020 Archives of Pharmacal Research Vol.43 No.12

Viruses have always been a class of pathogenicmicroorganisms that threaten the health and safety of humanlife worldwide. However, for a long time, the treatment ofviral infections has been slow to develop, and only a fewantiviral drugs have been using clinically. Compared withthese from terrestrial environments, marine-derived microorganismscan produce active substances with more novelstructures and unique functions. From 2015 to 2019, 89antiviral compounds of 8 structural classes have been isolatedfrom marine microorganisms, of which 35 exhibit anti-H1N1 activity. This review surveys systematically marinemicrobial-derived natural products with antiviral activityand illustrates the impact of these compounds on antiviraldrug discovery research.

Evaluation of the Biological Activities of Marine Bacteria Collected from Jeju Island, Korea, and Isolation of Active Compounds from their Secondary Metabolites

Kim, Hyun-Soo,Zhang, Chao,Lee, Ji-Hyeok,Ko, Ju-Young,Kim, Eun-A,Kang, Nalae,Jeon, You-Jin The Korean Society of Fisheries and Aquatic Scienc 2014 Fisheries and Aquatic Sciences Vol.17 No.2

To explore marine microorganisms with medical potential, we isolated and identified marine bacteria from floats, marine algae, animals, and sponges collected from Jeju Island, Korea. We isolated and identified 21 different strains from the marine samples by 16S rRNA analysis, cultured them in marine broth, and extracted them with ethyl acetate (EtOAc) to collect secondary metabolite fractions. Next, we evaluated their anti-oxidative and anti-inflammatory effects. Among the 21 strains, the secondary metabolite fraction of Bacillus badius had both strong antioxidant and anti-inflammatory activity, and thus was selected for further experiments. An antioxidant compound detected from the secondary metabolite fraction of B. badius was purified by preparative centrifugal partition chromatography (n-hexane:EtOAc:methanol:water, 4:6:4:6, v/v), and identified as diolmycin A2. Additionally, diolmycin A2 strongly inhibited nitric oxide production. Thus, we successfully identified a significant bioactive compound from B. badius among the bacterial strains collected from Jeju Island.

Original Article : Evaluation of the Biological Activities of Marine Bacteria Collected from Jeju Island, Korea, and Isolation of Active Compounds from their Secondary Metabolites

( Hyun Soo Kim ),( Chao Zhang ),( Ji Hyeok Lee ),( Ju Young Ko ),( Eun A Kim ),( Nalae Kang ),( You Jin Jeon ) 한국수산과학회(구 한국수산학회) 2014 Fisheries and Aquatic Sciences Vol.17 No.2

To explore marine microorganisms with medical potential, we isolated and identified marine bacteria from floats, marine algae, animals, and sponges collected from Jeju Island, Korea. We isolated and identified 21 different strains from the marine samples by 16S rRNA analysis, cultured them in marine broth, and extracted them with ethyl acetate (EtOAc) to collect secondary metabolite fractions. Next, we evaluated their anti-oxidative and anti-inflammatory effects. Among the 21 strains, the secondary metabolite fraction of Bacillus badius had both strong antioxidant and anti-inflammatory activity, and thus was selected for further experiments. An antioxidant compound detected from the secondary metabolite fraction of B. badius was purified by preparative centrifugal partition chromatography (n-hexane:EtOAc:methanol:water, 4:6:4:6, v/v), and identified as diolmycin A2. Additionally, diolmycin A2 strongly inhibited nitric oxide production. Thus, we successfully identified a significant bioactive compound from B. badius among the bacterial strains collected from Jeju Island.

Morphological Diversity of Marine Microorganisms on Different Isolation Media

ShinHyePark,KaeKyoungKwon,Deuk-SooLee,HongKumLee 한국미생물학회 2002 The journal of microbiology Vol.40 No.2

Isolation frequency of microorganisms from marine sources was examined with different media and samples collected from the coastal area of Cheju Island. From sea water samples, about 1% of microorganisms from the total number of bacteria were recovered. Microorganisms were cultured at the much lower frequency of 10-4-10-6 from other marine sources, such as sediment, sponges and corals. The frequency of duplicated isolation was examined with 140 morphologically different colonies isolated on different media. Fourteen percent of them exhibited the same morphology on two different media. The duplication frequency of the isolates among three different media was 33%.

Screening of Marine Microbial Extracts for Tyrosine Phosphatase 1B Inhibitors

Sohn, Jae-Hak,Park, Sun Jung,Seo, Changon,Chun, Bokyung,Oh, Hyuncheol The Korean Society for Marine Biotechnology 2007 한국해양바이오학회지 Vol.2 No.4

Protein tyrosine phosphatase 1B (PTP1B) acts as a negative regulator of insulin signaling, and selective inhibition of PTP1B has served as a potential drug target for the treatment of type 2 diabetes. As part of our searching for PTP1B inhibitors from natural products, the extracts of marine microorganisms were screened for the inhibitory effects on the activity of protein tyrosine phosphatase 1B (PTP1B). Among the tested 304 extracts, 29 extracts exhibited inhibition rate ranging 40.1 - 83.6 % against PTP1B at the concentration level of $30{\mu}g/mL$.

Optimal Conditions for the Production of Exopolysaccharide by Marine Microoranism Hahella chejebsis

Ko, Sung-Hwan,Lee, Hyun-Sang,Park, Shin hye,Lee, Hong-Kum The Korean Society for Biotechnology and Bioengine 2000 Biotechnology and Bioprocess Engineering Vol.5 No.3

A marine microorganism, strain 96CJ10356 produced exopolysaccharide, designated as EPS-R. To optimize culmize culture conditions for the production of EPS-R, carbon and nitrogen sources, mineral salts, temperature, and pH were exmined. From this study, STN medium for the production of EPS-R was suggested as follows; sucrose 20g, typtone 10g, NaCl 10g, MgSO45g, CaCl21g, KH2PO4 76mg, K2HPO4 83mg, FeCl2 5mg, MnCl2 1mg, NaMoO4 1mg, and ZnCl2 1mg per liter at pH 7.0. About 9.23g/L of EPS-R was obtained from STN medium after cultivation for 120h at $25^{\circ}C$ in a 5-liter jar fermentor with an aearation rate of 0.17 vvm. Apparent viscosity and flocculation activity of the culture broth were increased with the production of EPS-R and the maximal values were 415 cP and 1400 unit/mL against 0.5% activated carbon, respectively.