Research

Research Overview

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. 

Representative Publications

1. Natural Product Biosynthesis.

 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

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.

Zou, Y., Garcia-Borras, M., Tang, M-C., Hirayama, Y., Li, D., Li, L., Watanabe, K., Houk, K. N.*, Tang, Y.*, “Enzyme-Catalyzed Cationic Epoxide Rearrangements in Quinolone Alkaloid Biosynthesis.” Nat. Chem. Biol. 2017, 13, 325-332. Link

Tang, M-C.,# Zou, Y.,# Watanabe, K., Walsh, C. T.*,   Tang, Y.* "Oxidative Cyclization in Natural Product Biosynthesis." 2017, Chem. Rev. 117, 5226–5333. Link

Ma, S. A., Li, J., Choi, J. W., Zhou, H., Lee, M., Moorthie, V., Xie, X., Kealey, J. T., Da Silva, N. A., Vederas, J. C.*, Tang, Y.* “Complete Reconstitution of a Highly-Reducing Iterative Polyketide Synthase.” Science 2009, 326, 589-592. Link

2. Biocatalysis, Protein Engineering and Metabolic Engineering

Harvey, C.#, Tang, M-C.#, (Stanford/UCLA U01 Team), Tang, Y., Hillenmeyer, M. E.* “HEx: a heterologous expression platform for the discovery of fungal natural products.” bioRxiv, 2018, https://doi.org/10.1101/247940. Link  Science Advances, 2018, DOI: 10.1126/sciadv.aar5459. Link

Walsh, C. T.*, Tu, B. P.*, Tang, Y.*, "Eight Kinetically Stable but Thermodynamically Activated Molecules that Power Cell Metabolism." Chem. Rev. 2018, 118, 1460-1494.  Link

Billingsley, J. M., DeNicola, A. B., Barber, J. S., Tang, M-C., Horecka, J., Chu, A., Garg, N. K., Tang, Y.*, “Engineering the Biocatalytic Selectivity of Iridoid Production in Saccharomyces cerevisiae.” Metab. Eng. 2017, 44, 117-125. Link

Jiménez-Osés, G.; Osuna, S.; Gao, X.;  Sawaya, M. R.;Gilson, L.; Collier, S. J.;Huisman, G. W.*; Yeates, T. O.*; Tang, Y.*; Houk, K. N.* “The Role of Distant Mutations and Allosteric Regulation on LovD Active Site Dynamics.” Nat. Chem. Biol. 2014, 10, 431–436. Link

3. Biomaterials

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