My research lab is interested in natural product biosynthesis and biocatalysis. In the natural product area, we are interested in elucidating biosynthetic pathways of polyketides, nonribosomal peptides and related compounds. Our goal is to understand the biochemical and structural basis of different enzymes encoded in these pathways. In particular, we are studying the biosynthesis of aromatic polyketides from Streptomyces and iteratively biosynthesized compounds from filamentous fungi. By accumulating biosynthetic knowledge and enzymatic tools, we aim towards the engineered biosynthesis of unnatural natural products through combinatorial biosynthesis.
In the biocatalysis area, we build upon our knowledge from the fundamental studies and aim to discover and engineer enzymes that can be used in the synthesis and semisynthesis of pharmaceutical compounds. We have demonstrated the potential of this approach in establishing a biocatalytic approach for making the blockbuster drug simvastatin.
1. Genome Mining and Natural Product Biosynthesis.
Zhang, Y., Lin, W., Kerr, T., Garg, N. K., Tang, Y.* "Fragment-Guided Genome Mining of Octacyclic Cyclophane Alkaloids from Fungi." J. Am. Chem. Soc. 2024, 146, 23933–23942. Link
Yee, D. A. Niwa, K., Perlatti, B., Chen, M., Li, Y., Tang, Y.* "Genome Mining of Unknown Unknown Natural Products." Nat. Chem. Biol. 2023, 19, 633-640. Link
Yan, C. Han, W., Zhou, Q., Niwa, K. Tang, M. J., Burch, J. E., Zhang, Y., Delgadillo, D. A., Sun, Z., Wu, Z., Jacobsen, S. E., Nelson, H. M., Houk, K. N., Tang, Y.* "Genome Mining from Agriculturally Relevant Fungi Led to a d-Glucose Esterified Polyketide with a Terpene-like Core Structure." 2023, J. Am. Chem. Soc. 145, 25080–25085. Link
Yan, Y,# Liu, Q.#, Zang, X.#, Yuan, S., Bat-Erdene, U., Nguyen, C. Gan, J., Zhou, J.*, Jacobsen, S. E.*, Tang, Y.*, " Resistance-Gene Directed Discovery of a Natural Product Herbicide with a New Mode of Action." Nature, 2018, 559, 415-418. Link
2. Enzyme Discovery and Biocatalysis
Chiang, C. Y. Ohashi, M.*, Le J., Chen, P., Zhou, Q., Qu, S., Bat-Urdene, U., Hematian, S., Rodriguez, J. A., Houk, K., N., Guo, Y., Loo, J. A., Tang, Y.*, "Copper-dependent halogenase catalyses unactivated C−H bond functionalization." Nature, 2025, 638, 126-132 . Link.
Chiang, C. Y., Ohashi, M.*, Tang, Y.* "Fungal RiPPs Side Chain Macrocyclization Catalyzed by Copper-Dependent DUF3328 Enzyme." J. Am. Chem. Soc. 2025, accepted. Link
Sun, Z.,#, Zang, X.,#, Zhou, Q., Ohashi, M., Houk, K. N.*, Zhou, J.*, Tang, Y.* "Iminium catalysis in natural Diels–Alderase." Nature Catalysis 2025, accepted. Link
Abad, A. Seshadri, K., Ohashi, M.*, Delgadillo, D., de Moraes, L., Nagasawa, K., Liu, M., Johnson, S., Nelson, H., Tang, Y.* "Discovery and Characterization of Pyridoxal 5’-Phosphate-Dependent Cycloleucine Synthases." 2024, J. Am. Chem. Soc. 146, 14672–14684. Link
Ohashi, M., Liu, F., Hai, Y., Chen, M., Tang, M-C., Yang, Z., Sato, M., Watanabe, K.*, Houk, K. N.*, Tang, Y.*, “SAM-Dependent Enzyme-Catalysed Pericyclic Reactions in Natural Product Biosynthesis.” Nature. 2017, 549, 502–506. Link.
3. Metabolic Engineering
Dror, M., Misa, J., Yee, D. A., Chu, A. M., Yu, R. K., Chan, B. B., Aoyama, L. S., Chaparala, A. P., O’Connor, S. E., Tang, Y.* “Engineered Biosynthesis of Plant Heteroyohimbine and Corynantheine Alkaloids in Saccharomyces cerevisiae.” 2024, J. Ind. Microb. Biotechnol. vol 51, kuad047. Link
Seshadri, K.#, Abad, A. N.#, Nagasawa, K. K.#, Yost, K., Johnson, C. W., Dror, M., Tang, Y.*, "Synthetic Biology in Natural Product Biosynthesis." Chem. Rev. 2025, accepted.
Yee, D. A., DeNicola, A. B., Billingsley, J. M., Creso, J. G., Subrahmanyam, V., Tang, Y.* " Engineered Mitochondrial Production of Monoterpenes in Saccharomyces cerevisiae." Metab. Eng. 2019, 55, 76-84. PMCID: PMC6717016 Link
4. Biomaterials (discontinued)
Zhao, M.; Liu, Y.; Hsieh, R.; Wang, N.; Tai, W.; Joo, K.; Wang, P.; Gu, Z.; Tang, Y.* “Clickable Protein Nanocapsules for Targeted Delivery of Recombinant p53 Protein.” J. Am. Chem. Soc. 2014, 136, 15319–15325. Link
Zhao, M., Hu, B., Gu, Z., Joo, K., Wang, P.*, Tang, Y.* “Degradable Polymeric Nanocapsule for Efficient Intracellular Delivery of a High Molecular Weight Tumor-Selective Protein Complex.” Nano Today. 2013, 8, 11-20. Link
Zhao, M., Biswas, A., Hu, B., Joo, K., Wang, P., Gu, Z., Tang, Y.* “Redox-Responsive Nanocapsules for Intracellular Protein Delivery.” Biomaterials 2011, 32, 5223-5230. Link