초록 ▼

-37과 91속 288종 999점의 칠레산 지의류 생물자원을 확보.
-19과 30속 60종 545균주 칠레산 지의류형성곰팡이 확보.
-지의체 및 지의류형성곰팡이 배양 산물로부터 methanol 추출물 356점, acetone 추출물 354점, ethyl acetate 분획물 38점, 물 분획물 38점으로 총 786점의 chemical library를 구축함.
-항생제 저항성 세균인 Enterococcus faecium와 Staphylococcus aureus에 대해 높은 항균활성을 보인 지의류로 Usnea sp.,

-37과 91속 288종 999점의 칠레산 지의류 생물자원을 확보.
-19과 30속 60종 545균주 칠레산 지의류형성곰팡이 확보.
-지의체 및 지의류형성곰팡이 배양 산물로부터 methanol 추출물 356점, acetone 추출물 354점, ethyl acetate 분획물 38점, 물 분획물 38점으로 총 786점의 chemical library를 구축함.
-항생제 저항성 세균인 Enterococcus faecium와 Staphylococcus aureus에 대해 높은 항균활성을 보인 지의류로 Usnea sp., Bryoria sp., Tuckermannopsis chlorophylla, Mobergia sp., Usnea durietizii 확인.
-항암 활성이 우수한 physciosporin 및 virensic acid 2개 물질 확보와 salazinic acid, gyrophoric acid, Thamnolic acid, Divaricatic acid 및 Nordivarticatic acid 등dml 화합물을 확인. 이 중에서 항암활성이 가장 높은 화합물은 physciosporin으로 확인.
-Physciosporin의 항암기작은 고농도에서 세포계획사(apoptosis)에 의해 암세포를 사멸시키며, 대장암 줄기세포에 대한 저농도에서의 항암효과는 암 줄기세포의 Hh signaling과 Notch1 signaling에 모두 영향을 주지만 Notch1 signaling에 더 많은 영향을 주어 암 줄기세포의 재생, 분화, 전이를 억제하는 것으로 확인.
-세계 최초로 항암활성이 우수한 Rhizoplaca melanophthalma 지의류형성곰팡이의 전체 유전체분석을 완료하고, 이로부터 16개 PKS 유전자 확보. 이들 유전자의 이형질전환체 개발을 완료하였으며, 이형질 전환체로부터 물질 생산 확인.
-지의류 생체를 immobilized cell system에 적용하여 생물전환기술을 통한 지의류 물질 대량생산이 현실적 불가능하다는 결과를 도출함으로서 현재 진행 중인 이형질 전환체 발현 기술의 개발 타당성을 확인하는 계기가 되었음.

Abstract ▼

This study was conducted to find leading compounds for novel drugs using Chilean lichen bioresources. Total 999 lichen specimens were collected from several parts of Chile and 288 lichen species were identified. Using the lichen samples, total 545 lichen-forming fungi were isolated. Total 786 chemic

This study was conducted to find leading compounds for novel drugs using Chilean lichen bioresources. Total 999 lichen specimens were collected from several parts of Chile and 288 lichen species were identified. Using the lichen samples, total 545 lichen-forming fungi were isolated. Total 786 chemical extracts were prepared for Chilean lichen chemical library using lichen thalli and lichen-forming fungi. Bioactivity of antimicrobial, antifibrinolysis and anticancer were screened using the chemical library. Acetone extract of Usnea sp., Bryoria sp., Tuckermannopsis chlorophylla, Mobergia sp., Usnea durietizii showed strong antimicrobial activity against antibiotic resistant pathogenic bacteria. Pseudocyphellaria granulata showed potent anticancer activity against several human cancer cell lines and apoptosis was proposed to be main cause of cancer cell death at lethal dosage. Two compounds of physciosporin and virensic acid were identified from the lichen. Among them, physciosporin were proved to be a causal agent of anticancer activity of the lichen. Physciosporin also exerted inhibitory effects on human colon cancer stem cell at sub-lethal dosage. Growth, differentiation and metastasis of the cancer stem cell was inhibited through blocking of Hh signaling and Notch1 signaling, and the latter was more sensitive to the former. Whole genome sequence of Rhizoplaca melanophthalma lichen-forming fungus was completed, and 16 PKS (polyketide synthase) genes were identified from the genome sequence. Lichen-forming fungal PKS genes were successfully transformed to Aspergillus nidulas. Novel compounds were produced through heterologus expression in the transformed A. nidulans and their chemical structures is under identification. The results suggest that lichen substances of chilean lichens can be promising natural substances for pharmaceutical use such as anticancer. Especially, physciosporin can be used as a leading compound to develop novel anticancer drugs which can kill cancer cells and inhibit metastasis of cancer stem cell. All bioresources obtained from the project were deposited in Korea lichen and allied bioresource center (KOLABIC) for public use.