(1) Development and application of the bioactive agents from marine bioresources
(2) Microbial fermentation and application
(3) Biosynthetic pathway of the active principles
Lab Research Introduction(A) Over half of the clinically used drugs were developed from unaltered natural products (NP) or synthetic entities with NP pharmacophores. Marine NP were the secondary metabolites from marine organisms with highly diversified structural features, unique skeletons, and varied bioactivities that keep the chemists and pharmacologists being intrigued. In the recent past, we have constructed a fermentation library by over 1,000 strains of marine algicolous fungi. Several series of novel bioactive compounds have been isolated and identified from the fungal strains as monitored and selected from the library based on results of the antimicrobial assay. Subsequently, some compounds with significant bioactivities could possibly be developed as natural antibiotics for aquaculture, and even put into application hopefully.
(B) The most important achievement on the natural product research was the discovery of antroquinonols from a local medicinal fungus Antrodia cinnamomea. These compounds have been proved to exhibit broad spectrum of bioactivities, and antroquinonol A is now conducted four clinical trials for four indications including hyperlipidemia, non-small lung cancer, pancreatic neoplasm, and anti-HBV. Hope this compound can be developed as drugs eventually. Additionally, the functional genome and biosynthesis pathway of the cylcohexenone moiety of antroquinonols has been disclosed by gene deletion and chemical supplementation, and the study on mass production of these compounds by heterogeneous expression on yeast or E. coli is now under way.
SCI papers(*corresponding author)
1.Chen M.-C., G.-J. Wang, Y.-H. Kuo, Y.-H. Chiang, T.-Y. Cho, Y.-M. Ju, T.-H. Lee,* 2018, Isoprenyl Phenolic Ethers from the Termite Nest-Derived Medicinal Fungus Xylaria fimbriata. J. Food Drug Anal. (in press)
2.Lin F.-L., J.-D. Ho, Y.-W. Cheng, G. C. Y. Chiou, J.-L. Yen, H.-M. Chang, T.-H. Lee,* G. Hsiao,* 2018, Theissenolactone C exhibited ocular protection of endotoxin-induced uveitis by attenuating ocular inflammatory responses and glial activation. Front. Pharmacol. 9:326.
3.Chang J.-C., G. Hsiao, R.-K. L., Y.-H. Kuo, Y.-M. Ju, T.-H. Lee,* 2017, Bioactive Constituents from the Termite Nest-Derived Medicinal Fungus Xylaria nigripes. J. Nat. Prod. 80: 38-44.
4.Yu P.-W., T.-Y. Cho, R.-F. Liou, S.-S. Tzean,* T.-H. Lee,* 2017, Identification of the orsellinic acid synthase PKS63787 for the biosynthesis of antroquinonols in Antrodia cinnamomea. Appl. Microbiol. Biotech. 101: 4701-4711.
5.Hsiao G., W.-C. Chi, K.-L. Pang, J.-J. Chen, Y.-H. Kuo, Y.-K. Wang, H.-J. Cha, S.-C. Chou, T.-H. Lee,* 2017, Hirsutane-type Sesquiterpenes with Inhibitory Activity of Microglial Nitric Oxide Production from the Red Alga-derived Chondrostereum sp. NTOU4196. J. Nat. Prod. 80: 1615-1622.
6.Chen M.-C., T.-Y. Cho, Y.-H. Kuo, T.-H. Lee,* 2017, Bioactive meroterpenoids from a Medicinal Fungus Antrodia cinnamomea. J. Nat. Prod. 80: 2439‒2446.
7.Lee T.-H., C.-C. Hsu, G. Hsiao, J.-Y. Fang, W.-M. Liu, C.-K. Lee, 2016, Anti-MMP-2 activity and skin-penetrating capability of the chemical constituents from Rhodiola rosea. Planta Med. 82: 698-704.
8.Cho T.-Y., G.-J. Wang, Y.-M. Ju, M.-C. Chen, T.-H. Lee,* 2016, Chemical Constituents from Termite-Associated Xylaria acuminatilongissima YMJ623. J. Chin. Chem. Soc. 63: 404-409.
9.Yu P.-W., Y.-C. Chang, R.-F. Liou, T.-H. Lee,* S.-S. Tzean,* 2016, pks63787, A Polyketide Synthase Gene Encodes the Biosynthesis of Benzenoids in the Medicinal Mushroom Antrodia cinnamomea. J. Nat. Prod. 79: 1485-1491.
10.Lee M.-S., C.-J. Hsiao, Y.-M. Ju, Y.-H. Kuo, R.-K. Lin, T.-H. Lee,* 2016, Terpenoids from the Fermented Broths of Coprinellus radians. Nat. Prod. Commun. 11: 1229-1230.
11.Lee M.-S., G.-J. Wang, K.-L. Pang, C.-K. Lee, Y.-H. Kuo, R.-K. Lin,* T.-H. Lee,* 2016, Angiogenesis inhibitors and anti-inflammatory agents from Phoma sp. NTOU4195. J. Nat. Prod. 79: 2983-2990.
12.Lee T.-H., M.-S. Lee, H.-H. Ko, J.-J. Chen, H.-S. Chang, M.-H. Tseng, S.-Y. Wang, C.-C. Chen, Y.-H. Kuo,* 2015, New Furanone and sesquiterpene from the pericarp of Calocedrus formosana Florin. Nat. Prod. Commun. 10: 845-846.
13.Chang Y. C., C.-K. Lu, Y.-R. Chiang, G.-J. Wang, Y.-M. Ju, Y.-H. Kuo, T. H. Lee,* 2014, Diterpene glycosides and polyketides from Xylotumulus gibbisporus. J. Nat. Prod. 77: 751-7.
14.Chen J. J., S. W. Wang, H. Y. Hsiao, Y. M. Ju, T. H. Lee,* 2014, Aliphatic phenolic ethers from Trichobotrys effusa. J. Nat. Prod. 77: 1097-1101.
15.Hsiao, Che-Jen, G. Hsiao, W.-L. Chen, S.-W. Wang, C.-P. Chiang, L.-Y. Liu, J.-H. Guh, T.-H. Lee,* C.-L. Chung,* 2014, Cephalochromin from Cosmospora vilior Induces G0/G1 Cell Cycle Arrest and Apoptosis in A549 Human Non-Small Cell Lung Cancer Cells by Inflicting Mitochondrial Disruption. J. Nat. Prod. 77: 758-765.
16.Lee T.-H., Y.-C. Chen, T.-L. Hwang, C.-W. Shu, P.-J. Sung, Y.-P. Lim, W.-L. Kuo, J.-J. Chen, 2014, New isoflavones and anti-inflammatory constituents from the fruits of Cnidium monnieri. Int. J. Mol. Sci. 15: 9566-78
17.Lee T.-H., C.-C. Chen, J.-J. Chen, H.-F. Liao, H.-S. Chang, P.-J. Sung, M.-H. Tseng, S.-Y. Wang, H.-H. Ko, Y.-H. Kuo,* 2014, New and Cytotoxic Components from Antrodia camphorata. Molecules 19, 21378‒21385.
Offer CourseSpectroscopic analysis of natural compounds
Natural product chemistry
Techniques of metabolomic analysis
Ph.D. & Master Seminar