Research

Natural products (NPs) have been an important source of molecules in drug discovery and development. Their diversity scaffolds and semisynthetic derivatives provide new chemical entities (NCEs) and exhibit variety of biological activities with pharmacological potentials. Recent advances in molecular biology, bioinformatics and whole-genome sequencing provided great advances in understanding the genetic and enzymatic basis of natural product biosynthesis.

Our research consists of the following topics. Each of these topics can be standalone but is at the same time interconnected with each other.

  1. Discovery of bioactive natural products based on activity-guided screening.
  2. Targeted gene cluster discovery and biosynthetic study of bioactive NPs.
  3. Discovery of new NPs by genome mining in microorganisms.
  4. Combinatorial biosynthesis in heterologous expression systems.
Degrees and Positions Held
Positions Held
  • 2015 – present   Assistant Research Fellow, Institute of Biological Chemistry, Academia Sinica
  • 2012 – 2015   Postdoctoral researcher, Department of Chemical and Biomolecular Engineering, University of California, Los Angeles
  • 2011 – 2012   Postdoctoral researcher, School of Pharmacy, National Taiwan University
Degrees
  • 2006 – 2011   Ph.D., School of Pharmacy, National Taiwan University
  • 2004 – 2006   M.S., School of Pharmacy, National Taiwan University
  • 2000 – 2004   B.S., School of Pharmacy, Taipei Medical University
Selected Publications
Lai CY, Lo IW, Hewage RT, Chen YC, Chen CT, Lee CF, Lin S, Tang MC, Lin HC
Angewandte Chemie-International Edition (2017)
Lin, H. C.; McMahon T. C.; Patel, A.; Corsello, M.; Simon, A.; Xu, W.; Zhao, M.; Houk, K. N.; Garg, N. K.; Tang, Y
J. Am. Chem. Soc. (2016)
Tang, M. C., Lin, H. C., Li, D., Zou, Y., Li, J., Xu, W., Cacho, R. A., Hillenmeyer, M., Garg, N. K., Tang, Y.
J. Am. Chem. Soc. (2015)
Mao, X. M., Zhan, Z. J., Grayson, M. N., Tang, M. C., Xu, W., Li, Y. Q., Yin, W. B., Lin, H. C., Chooi, Y. H., Houk, K. N., Tang, Y.
J. Am. Chem. Soc. (2015)
Lin, H. C.; Chou, G.; Chooi, Y. H.; McMahan, T. C.; Xu, W.; Garg, N. K.; Tang, Y.
Angew. Chem. Int. (2015)
Lin, H. C.; Yuta, T., Dhingra, S., Xu, W.; Fukutomi, M.; Chooi, Y. H.; Cane, D. E.; Calvo, A. M; Watanabe, K.; Tang, Y.
J. Am. Chem. Soc. (2014)
Lin, H. C.; Chooi, Y. H.; Dhingra S.; Xu, W.; Calvo, A. M.; Tang Y.
J. Am. Chem. Soc. (2013)
Lin, H. C.; Lee, S. S.
J. Nat. Prod. (2012)
Lin, H. C.; Tsai, S. F.; Lee, S. S.
J. Chin. Chem. Soc. (2011)
Publications List
  1. 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."
  2. Tran PN, Yen MR, Chiang CY, (Lin HC)*, Chen PY*  (2019-04)  Applied Microbiology and Biotechnology  103(8), 3277–3287  "Detecting and prioritizing biosynthetic gene clusters for bioactive compounds in bacteria and fungi."
  3. (Lin HC*), Hewage RT, Lu YC, Chooi YH  (2019-02)  Organic & biomolecular chemistry  17(5), 1027-1036  "Biosynthesis of bioactive natural products from Basidiomycota."
  4. 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."
  5. 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."
  6. 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."
  7. (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"
  8. 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."
  9. 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."
  10. (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"
  11. 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."
  12. 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"
  13. 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."
  14. 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"
  15. (Lin HC), Lee SS  (2012-10)  Journal of natural products  75(10), 1735-1743  "Dibenzocycloheptanoids from the leaves of Cinnamomum subavenium."
  16. (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"
  17. (Lin HC), Lee SS  (2010-08)  Journal of natural products  73(8), 1375-1380  "Proanthocyanidins from the leaves of Machilus philippinensis."
  18. Lee SS, (Lin HC), Chen CK  (2008-09)  Phytochemistry  69(12), 2347-2353  "Acylated flavonol monorhamnosides, alpha-glucosidase inhibitors, from Machilus philippinensis."

Natural products (NPs) have been an important source of molecules in drug discovery and development. Their diversity scaffolds and semisynthetic derivatives provide new chemical entities (NCEs) and exhibit variety of biological activities with pharmacological potentials. Recent advances in molecular biology, bioinformatics and whole-genome sequencing provided great advances in understanding the genetic and enzymatic basis of natural product biosynthesis.

Our research consists of the following topics. Each of these topics can be standalone but is at the same time interconnected with each other.

  1. Discovery of bioactive natural products based on activity-guided screening.
  2. Targeted gene cluster discovery and biosynthetic study of bioactive NPs.
  3. Discovery of new NPs by genome mining in microorganisms.
  4. Combinatorial biosynthesis in heterologous expression systems.
Positions Held
  • 2015 – present   Assistant Research Fellow, Institute of Biological Chemistry, Academia Sinica
  • 2012 – 2015   Postdoctoral researcher, Department of Chemical and Biomolecular Engineering, University of California, Los Angeles
  • 2011 – 2012   Postdoctoral researcher, School of Pharmacy, National Taiwan University
Degrees
  • 2006 – 2011   Ph.D., School of Pharmacy, National Taiwan University
  • 2004 – 2006   M.S., School of Pharmacy, National Taiwan University
  • 2000 – 2004   B.S., School of Pharmacy, Taipei Medical University
Lai CY, Lo IW, Hewage RT, Chen YC, Chen CT, Lee CF, Lin S, Tang MC, Lin HC
Angewandte Chemie-International Edition (2017)
Lin, H. C.; McMahon T. C.; Patel, A.; Corsello, M.; Simon, A.; Xu, W.; Zhao, M.; Houk, K. N.; Garg, N. K.; Tang, Y
J. Am. Chem. Soc. (2016)
Tang, M. C., Lin, H. C., Li, D., Zou, Y., Li, J., Xu, W., Cacho, R. A., Hillenmeyer, M., Garg, N. K., Tang, Y.
J. Am. Chem. Soc. (2015)
Mao, X. M., Zhan, Z. J., Grayson, M. N., Tang, M. C., Xu, W., Li, Y. Q., Yin, W. B., Lin, H. C., Chooi, Y. H., Houk, K. N., Tang, Y.
J. Am. Chem. Soc. (2015)
Lin, H. C.; Chou, G.; Chooi, Y. H.; McMahan, T. C.; Xu, W.; Garg, N. K.; Tang, Y.
Angew. Chem. Int. (2015)
Lin, H. C.; Yuta, T., Dhingra, S., Xu, W.; Fukutomi, M.; Chooi, Y. H.; Cane, D. E.; Calvo, A. M; Watanabe, K.; Tang, Y.
J. Am. Chem. Soc. (2014)
Lin, H. C.; Chooi, Y. H.; Dhingra S.; Xu, W.; Calvo, A. M.; Tang Y.
J. Am. Chem. Soc. (2013)
Lin, H. C.; Lee, S. S.
J. Nat. Prod. (2012)
Lin, H. C.; Tsai, S. F.; Lee, S. S.
J. Chin. Chem. Soc. (2011)
  1. 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."
  2. Tran PN, Yen MR, Chiang CY, (Lin HC)*, Chen PY*  (2019-04)  Applied Microbiology and Biotechnology  103(8), 3277–3287  "Detecting and prioritizing biosynthetic gene clusters for bioactive compounds in bacteria and fungi."
  3. (Lin HC*), Hewage RT, Lu YC, Chooi YH  (2019-02)  Organic & biomolecular chemistry  17(5), 1027-1036  "Biosynthesis of bioactive natural products from Basidiomycota."
  4. 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."
  5. 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."
  6. 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."
  7. (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"
  8. 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."
  9. 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."
  10. (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"
  11. 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."
  12. 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"
  13. 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."
  14. 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"
  15. (Lin HC), Lee SS  (2012-10)  Journal of natural products  75(10), 1735-1743  "Dibenzocycloheptanoids from the leaves of Cinnamomum subavenium."
  16. (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"
  17. (Lin HC), Lee SS  (2010-08)  Journal of natural products  73(8), 1375-1380  "Proanthocyanidins from the leaves of Machilus philippinensis."
  18. Lee SS, (Lin HC), Chen CK  (2008-09)  Phytochemistry  69(12), 2347-2353  "Acylated flavonol monorhamnosides, alpha-glucosidase inhibitors, from Machilus philippinensis."