中央研究院 生物化學研究所

研究領域與專長

天然物(Natural products, NPs)在藥物開發與發展的過程中，對於藥物來源扮演著重要的角色，天然物的結構多樣性及其半合成衍生物提供了新化學物質(new chemical entities, NCEs)，並具有不同生物活性及藥理潛力。近年來，隨著分子生物、生物資訊和基因體定序科技的進步，對於以基因和蛋白質層面研究天然物的生合成，具有重大的發展及應用。

我們實驗室的研究方向可分為下列幾項，各項可為獨立研究題材或互為相輔方向：

1. 新穎活性天然物的分離與鑑定−以活性測試為導向
2. 活性天然物生物合成研究，其中包括瞭解基因、酵素功能以及催化機轉
3. 利用基因採礦，探索”沉默”基因簇編碼的活性化合物
4. 以異源性表達進行組合式生物合成

更多實驗室資訊請見: https://sites.google.com/site/hsiaochinglab/home

學經歷

• 2006 – 2011   博士, 藥學系, 臺灣大學
• 2004 – 2006   碩士, 藥學系, 臺灣大學
• 2000 – 2004   學士, 藥學系, 臺北醫學大學

• 2020 – 迄今   副研究員, 中央研究院生物化學研究所
• 2015 – 2020   助研究員, 中央研究院生物化學研究所
• 2012 – 2015   博士後研究, Department of Chemical and Biomolecular Engineering, University of California, Los Angeles
• 2011 – 2012   博士後研究, 臺灣大學藥學系

主要著作

The Biosynthetic Gene Cluster of Mushroom-Derived Antrocin Encodes Two Dual-Functional Haloacid Dehalogenase-like Terpene Cyclases.  
Chen TH, Chen CT, Lee CF, Huang RJ, Chen KL, Lu YC, Liang SY, Pham MT, Rao YK, Wu SH, Chein RJ, , Lin HC*  
Angewandte Chemie-International Edition (2023)

Biosynthesis of Piperazine-Derived Diazabicyclic Alkaloids Involves a Nonribosomal Peptide Synthetase and Subsequent Tailoring by a Multifunctional Cytochrome P450 Enzyme.     
Pham MT, Chen SR, Liang SY, Cheng YB, Lin HC*   
Organic letters (2022)

An Enzyme-Mediated Aza-Michael Addition Is Involved in the Biosynthesis of an Imidazoyl Hybrid Product of Conidiogenone B.     
Hewage RT, Huang RJ, Lai SJ, Lien YC, Weng SH, Li D, Chen YJ, Wu SH, Chein RJ*, Lin HC*   
Organic letters (2021)

Discovery of a Dual Function Cytochrome P450 that Catalyzes Enyne Formation in Cyclohexanoid Terpenoid Biosynthesis.     
Chen YR, Naresh A, Liang SY, Lin CH, Chein RJ, Lin HC*   
Angewandte Chemie-International Edition (2020)

Enzyme-Catalyzed Azepinoindole Formation in Clavine Alkaloid Biosynthesis.     
Chen KL, Lai CY, Pham MT, Chein RJ, Tang Y, Lin HC*   
Organic letters (2020)

The Biosynthesis of Norsesquiterpene Aculenes Requires Three Cytochrome P450 Enzymes to Catalyze a Stepwise Demethylation Process.     
Lee CF, Chen LX, Chiang CY, Lai CY, Lin HC*   
Angewandte Chemie-International Edition (2019)

Biosynthesis of Complex Indole Alkaloids: Elucidation of the Concise Pathway of Okaramines.     
Lai CY, Lo IW, Hewage RT, Chen YC, Chen CT, Lee CF, Lin S, Tang MC, Lin HC*     
Angewandte Chemie-International Edition (2017)

著作列表

1. Hewage RT, Tseng CC, Liang SY, Lai CY, (Lin HC)*  (2023-02)  Philosophical Transactions of the Royal Society B-Biological Sciences  378(1871), 20220033  "Genome mining of cryptic bisabolenes that were biosynthesized by intramembrane terpene synthases from Antrodia cinnamomea."
   
2. Chen TH, Chen CT, Lee CF, Chen RC, Chen KL, Lu YC, Liang SY, Pham MT, Rao YK, Wu SH, Chein RJ, (Lin HC)*  (2023-02)  Angewandte Chemie-International Edition  62(9), e202215566  "The Biosynthetic Gene Cluster of Mushroom-Derived Antrocin Encodes Two Dual Functional Haloacid Dehalogenase-Like Terpene Cyclases."
   
3. Pham MT, Chen SR, Liang SY, Cheng YB, (Lin HC)*  (2022-06)  Organic letters  24(22), 4064-4069  "Biosynthesis of Piperazine-Derived Diazabicyclic Alkaloids Involves a Nonribosomal Peptide Synthetase and Subsequent Tailoring by a Multifunctional Cytochrome P450 Enzyme."
   
4. Hewage RT, Huang RJ, Lai SJ, Lien YC, Weng SH, Li D, Chen YJ, Wu SH, Chein RJ*, (Lin HC)*  (2021-03)  Org Lett.  23(5), 1904-1909  "An Enzyme-Mediated Aza-Michael Addition Is Involved in the Biosynthesis of an Imidazoyl Hybrid Product of Conidiogenone B."
   
5. Yan Y, Zang X, Jamieson CS, (Lin HC), Houk KN, Zhou JH, Tang Y  (2020-09)  Chemical Science  11(35), 9554-9562  "Biosynthesis of the fungal glyceraldehyde-3-phosphate dehydrogenase inhibitor heptelidic acid and mechanism of self-resistance."
   
6. Chen YR, Naresh A, Liang SY, Lin CH, Chein RJ, (Lin HC)  (2020-08)  Angewandte Chemie-International Edition  59(32), 13537-13541  "Discovery of a Dual Function Cytochrome P450 that Catalyzes Enyne Formation in Cyclohexanoid Terpenoid Biosynthesis."
   
7. Chen KL, Lai CY, Pham MT, Chein RJ, Tang Y, (Lin HC)*  (2020-04)  Organic letters  22(8), 3302-3306  "Enzyme-Catalyzed Azepinoindole Formation in Clavine Alkaloid Biosynthesis."
   
8. Lee CF, Chen LX, Chiang CY, Lai CY, (Lin HC)  (2019-12)  Angewandte Chemie - International Edition  58(51), 18414-18418  "The Biosynthesis of Norsesquiterpene Aculenes Requires Three Cytochrome P450 Enzymes to Catalyze a Stepwise Demethylation Process."
   
9. Tran PN, Yen MR, Chiang CY, (Lin HC)*, Chen PY*  (2019-03)  Applied Microbiology and Biotechnology  103(8), 3277–3287  "Detecting and prioritizing biosynthetic gene clusters for bioactive compounds in bacteria and fungi."
   
10. (Lin HC*), Hewage RT, Lu YC, Chooi YH  (2019-02)  Organic & biomolecular chemistry  17(5), 1027-1036  "Biosynthesis of bioactive natural products from Basidiomycota."
    
11. Harvey CJB, Tang M, Schlecht U, Horecka J, Fischer CR, (Lin HC), Li J, Naughton B, Cherry J, Miranda M, Li YF, Chu AM, Hennessy JR, Vandova GA, Inglis D, Aiyar RS, Steinmetz LM, Davis RW, Medema MH, Sattely E, Khosla C, St Onge RP, Tang Y, Hillenmeyer ME  (2018-04)  Science Advances  4(4), eaar5459  "HEx: A heterologous expression platform for the discovery of fungal natural products."
    
12. Lai CY, Lo IW, Hewage RT, Chen YC, Chen CT, Lee CF, Lin S, Tang MC, (Lin HC*)  (2017-08)  Angewandte Chemie-International Edition  56(32), 9478-9482  "Biosynthesis of Complex Indole Alkaloids: Elucidation of the Concise Pathway of Okaramines."
    
13. Zhao M, (Lin HC), Tang Y  (2016-07)  The Journal of antibiotics  69(7), 571-573  "Biosynthesis of the alpha-nitro-containing cyclic tripeptide psychrophilin."
    
14. (Lin HC), McMahon TC, Patel A, Corsello M, Simon A, Xu W, Zhao M, Houk KN, Garg NK, Tang Y  (2016)  Journal of the American Chemical Society  138(12), 4002-4005  "P450-Mediated Coupling of Indole Fragments To Forge Communesin and Unnatural Isomers"
    
15. Tang MC, (Lin HC), Li D, Zou Y, Li J, Xu W, Cacho RA, Hillenmeyer ME, Garg NK, Tang Y  (2015-11)  Journal of the American Chemical Society  137(43), 13724-13727  "Discovery of Unclustered Fungal Indole Diterpene Biosynthetic Pathways through Combinatorial Pathway Reassembly in Engineered Yeast."
    
16. Mao XM, Zhan ZJ, Grayson MN, Tang MC, Xu W, Li YQ, Yin WB, (Lin HC), Chooi YH, Houk KN, Tang Y  (2015-09)  Journal of the American Chemical Society  137(37), 11904-11907  "Efficient Biosynthesis of Fungal Polyketides Containing the Dioxabicyclo-octane Ring System."
    
17. (Lin HC), Chiou G, Chooi YH, McMahon TC, Xu W, Garg NK, Tang Y  (2015)  ANGEWANDTE CHEMIE-INTERNATIONAL EDITION  127(10), 3047-3050  "Elucidation of the Concise Biosynthetic Pathway of the Communesin Indole Alkaloids"
    
18. Zabala AO, Chooi YH, Choi MS, (Lin HC), Tang Y  (2014-07)  ACS chemical biology  9(7), 1576-1586  "Fungal polyketide synthase product chain-length control by partnering thiohydrolase."
    
19. Lin Hsiao-Ching, Tsunematsu Yuta, Dhingra Sourabh, Xu Wei, Fukutomi Manami, Chooi Yit-Heng, Cane David E., Calvo Ana M., Watanabe Kenji, Tang Yi  (2014)  Journal of the American Chemical Society  136(11), 4426-4436  "Generation of Complexity in Fungal Terpene Biosynthesis: Discovery of a Multifunctional Cytochrome P450 in the Fumagillin Pathway"
    
20. Dhingra S, Lind AL, (Lin HC), Tang Y, Rokas A, Calvo AM  (2013-10)  PloS one  8(10), e77147  "The fumagillin gene cluster, an example of hundreds of genes under veA control in Aspergillus fumigatus."
    
21. Lin Hsiao-Ching, Chooi Yit-Heng, Dhingra Sourabh, Xu Wei, Calvo Ana M., Tang Yi  (2013)  Journal of the American Chemical Society  135(12), 4616-4619  "The Fumagillin Biosynthetic Gene Cluster inAspergillus fumigatusEncodes a Cryptic Terpene Cyclase Involved in the Formation of β-trans-Bergamotene"
    
22. (Lin HC), Lee SS  (2012-10)  Journal of natural products  75(10), 1735-1743  "Dibenzocycloheptanoids from the leaves of Cinnamomum subavenium."
    
23. (Lin, H. C.), Tsai, S. F., Lee, S. S.  (2011-08)  Journal of the Chinese Chemical Society  58(4), 555-562  "Flavonoid Glycosides from the Leaves of Machilus philippinensis"
    
24. (Lin HC), Lee SS  (2010-08)  Journal of natural products  73(8), 1375-1380  "Proanthocyanidins from the leaves of Machilus philippinensis."
    
25. Lee SS, (Lin HC), Chen CK  (2008-09)  Phytochemistry  69(12), 2347-2353  "Acylated flavonol monorhamnosides, alpha-glucosidase inhibitors, from Machilus philippinensis."