Research Overview

    Natural products consistently provide unmatched molecular structural diversity for drug discovery in the pharmaceutical view. The oceans cover 70% of the Earth’s surface and harbor most of the planet’s biodiversity, which have received considerable attention as a resource for natural product discovery. Taiwan, surrounded by Taiwan Strait and Pacific Ocean, possesses abundant marine resources. Searching new bioactive principles from the unique Taiwanese resources by an efficient strategy is emergency and important for Taiwan biotechnology and pharmaceutical industries in future.

 a)  Establishing the de-replication strategy on rapidly searching novel bioactive natural products from marine microbes

    De-replication by modern analytical instruments, such as NMR and LC-MS/MS, has become a popular and powerful strategy for natural products research, especially, based on the established/commercial chemical database, such as Scifinder, MarinLit/Antimarin, and so on. Although these databases are very helpful for the identification of natural products to save time, scientists still need to put a lot of efforts in the time- and cost-consuming natural products isolation process to confirm their research results, accompanied with such de-replication process. On the other hand, following the advances of modern mass spectral analysis, the molecular networking analysis generated by the MS/MS data of microbial metabolites from colonies (without extraction) can successfully distinguish different groups of peptide compounds for studying microbial interaction and metabolomics. Furthermore, we also found this can also be used on the identification and grouping of small molecular metabolites of microbes. In the proposal, we would like to propose a new strategy on rapidly searching novel bioactive compounds from natural sources by using chemotype identification of microbes, peak library establishment and molecular networking analysis, coupling with bioactivity-guided fractionation isolation and spectral/chemical databases de-replication process. At the mean times, by the strategy mentioned above, we would like to explore the novel secondary metabolites of deep-sea marine microbes, such as Genera Bacillus and Streptomyces, and microbial symbionts, such as Genera Microbulbifer and Pseudovibrio, of marine invertebrates from the unexplored waters of Taiwan and investigate their anti-microbial and anti-cancer activities.

The work flowchart to search bioactive components from marine microbes.

Relevant Research Projects

1.  The study on the antibiotic and anti-inflammatory secondary metabolites from marine micro-organisms, supported by the grant from National Science Council (自海洋微生物獲取具抗生活性之天然產物，NSC 101-2320-B-110 -001).

2.  The study on the secondary metabolites from marine microorganisms and their modified analogues to inhibit opportunistic pathogens, supported by the grant from National Science Council (研究海洋微生物二次代謝物及其衍生物在抑制伺機性病菌之作用，NSC 102-2320-B-110 -002).

3.  The study on establishing the strategy on rapidly searching novel bioactive natural products from marine microbes by molecular networking, supported from Ministry of Science and Technology (利用質譜分子網絡等工具建立快速尋找新型海洋微生物活性天然產物之策略，MOST103-2628-B-110-001-MY3).

4.  The researches on the marine natural products with anti-microbial, anti-virual, and cytotoxic activities from symbiotic microbes in marine invertebrates (自海洋無脊椎共生微生物開發抗菌、抗病毒與細胞毒殺海洋活性天然物研究, MOST 105-2320-B-110 -002 -MY3)

 b) Study on Marine Microbial Ligands to complex with trace metals

    Trace metals play the important role in the growth of organisms on Earth, such as the redox centers of various enzymes. The trace metals all occur in picomolar to nanomolar quantities in the world’s oceans. Marine microorganisms are presented with unique challenges to obtain essential metal ions required to survive and thrive in the ocean. The production of organic ligands to complex transition metal ions is one strategy to both facilitate uptake of specific metals, such as iron, and to mitigate the potential toxic effects of other metal ions, such as copper.
    Taiwan is an island with high mountains and rivers cross the mountain areas, which take large amount rock and sand into ocean in seasons of falling rain. In addition, steel-slag disposal make unusual distributions of certain trace metals in Taiwan Strait. All of these phenomena affect the life cycle and distribution of marine microorganisms. In the proposal, we plan to decipher the chemical structures of organic ligands from the marine microorganisms and to clarify the metal speciation of these ligands and their bioavailability, which will be helpful for us to understand how ligands bind with and control metal speciation and cycling within the Earth's oceans.
 

Relevant Research Projects

1.  The study on the secondary metabolites from marine microbes as marine ligands to complexe with trace metals, supported by the grant from National Science Council (海洋微生物所產之二次代謝物做為海洋配體對微量金屬之螯合作用研究，NSC 102-2611-M-110 -008).

2.  The study on elucidating the relationship between trace metal and molecular networking, supported by the grant from Ministry of Science and Technology, supported from Ministry of Science and Technology (以海洋微生物代謝物分子網路建立其海洋配體與海洋微量金屬之關係，MOST 103-2611-M-110-006).

3.  The analysis of marine ligands from marine mircoorganism to chelate the trace metals on water in southern Taiwan, supported from Ministry of Science and Technology (台灣南部海域海洋微生物產螯合微量金屬之海洋配體分析，MOST 104-2611-M-110-021).

 c) Evaluation and Development of Marine Antifouling Agents

    Biofouling is the accumulation of marine organisms, including bacteria, algae, mollusks, polychaetes, ascidians, and barnacles on wetted surfaces of vessels and other man-made structures, which usually associate corrosions and damages. Since tributyl-tin (TBT) was globally banned in 2008 for its irreversible adverse effect on marine life, it is urgent for scientists to discover novel, effective and environmental-friendly antifouling agents. We have found several natural-occurring chemicals with antifouling activities from marine microorganisms, marine invertebrates, and terrestrial plants by testing on established bioassays, including antimicrobial, anti-biofilm forming and anti-barnacle settlement assays. Based on our preliminary results, we expect to discover more chemical agents with similar structural skeletons (pharmacophores) from various resources or synthesize their analogues for further bioassay screening. This study will offer more compounds with antifouling activities as options to apply in the paint/coating industries. All in all, the aim of this project is to search novel antifouling candidate agents from secondary metabolites of multiple sources based on the skeletons of compounds with known antifouling activities.

Searching a complex formula of anti-fouling agents.

Relevant Research Project

1.  Evaluation and Development of Antifouling Agents, supported by the grant from YUNG CHI PAINT & VARNISH MFG. CO.,LTD (NSC 101-2320-B-110 -001).

 d) Study on the Bioactive Components from Herbal Medicine

    Secondary metabolites, namely natural products, are the chemical compounds of metabolism that are not essential for normal growth, development or reproduction of an organism. Secondary metabolites should also include products of overflow metabolism as a result of nutrient limitation, or shunt metabolites produced during idiophase, defense mechanisms, regulator molecules, and so on. These metabolites also present multifunctions in the bodies of life organism, such as the signal transmitter.
      Based on our previous experience on the studies of bioactive compounds of folk medicines, we set two aims;

1. to isolate and purify the bioactive components or lead compounds of TCM / folk medicine (herb) / marine organisms by bioactivity-guided fractionation isolation, such as anti-cancer (cytotoxicity), anti-inflammatory effect, anti-diabetes, and so on. We also try to investigate the mechanism of actions of bioactive compounds or the modified analogues of lead compounds.

2. to investigate the bioactive compounds from TCM tonics to induce (manipulate) the “directed” differentiation of embryonic stem (ES) cells to promote the application of natural products or herb medicine in the regenerative medicine in the future.

Relevant Research Projects

1.  The study of anticancer components from Pterocarpus indicus wild, supported by the grant from National Science Council, 2005,08,01-2006,07,31  (NSC94-2320-B-041-011).

2.  The research on the anticancer and anti-inflammatory components of Cannabaceous plant, Humulus scandens, supported by the grant from National Science Council, 2006,08,01-2007,07,31 (NSC 95-2320-B-039-052).

3.  The development of cosmetic resources from Traditional Chinese Medicine, safflower, and relative researches, supported by the grant from National Science Council, 2006,05,01-2007,04,30 (NSC 95-2622-B-039-001-CC3).

4.  The investigation of functional properities of anti-cancer and anti-inflammatory components from Taiwanese folk medicine in the pathogenesis of pancreatic adenocarcinoma, supported by the grant from National Science Council, 2007,08,01-2008,07,31 (NSC 96-2320-B-039-025).

5.  The researches on the anti-inflammatory components from Formosan Folk medicine and the modification of these bioactive components, supported by the grant from National Science Council, 2008,08,01-2011,07,31 (NSC 97-2320-B-039-018-MY3).

6.  The study on the bioactive substances of Avicenia marina, Sesuvium portulacastrum, and Pittosporum moluccanum in Pingtung mangrove swamp, supported by the grant from National Science Council (NSC 100-2320-B-110 -004).