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. 

My lab has also recently become interested in research at the interface of nanotechnology, biomaterials and drug delivery.  In particular, we are conducting research towards the efficient delivery of various biological molecules to cells and model animals for applications in cancer therapy, imaging, vaccination and reprogramming.  These nascent efforts are performed in collaboration with various labs.

Representative Publications

1. Natural Product Biosynthesis.

Cacho, R. A. Chooi, Y., Zhou, H., Tang, Y.* “Complexity Generation in Fungal Polyketide Biosynthesis: a Spirocycle-Forming P450 in the Concise Pathway to the Antifungal Drug Griseofulvin.” ACS Chem. Biol. 2013, in press. Link

 

Wang, P., Bashiri, G., Gao, X., Sawaya, M. R. Tang, Y. * “Uncovering the Enzymes that Catalyze the Final Steps in Oxytetracycline Biosynthesis.” J. Am. Chem. Soc. 2013, 135, 7138-7141. Link

 

Chooi, Y.*, Tang, Y.* “Navigating the Fungal Polyketide Chemical Space: From Genes to Molecules.” J. Org. Chem. 2012, 77, 9933–9953. (invited perspective) 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 and Protein Engineering

 

Zhou, H., Gao, Z., Qiao, K., Wang, J., Vederas, J. C.*, Tang, Y.* “A fungal ketoreductase domain that displays substrate-dependent stereospecificity.” Nat. Chem. Biol. 2012, 9, 331-333. (Cover Story)  Link

 

Chooi, Y.*, Wang, P., Fan, J., Li, Y., Wu, K., Wang, P., Tang, Y.* “Characterization of a Group of Fungal Aromatic Polyketide Prenyl-transferases.” J. Am. Chem. Soc.  2012, 134, 9428–9437. Link

 

Gao, X., Xie, X., Pashkov, I., Sawaya, R. M., Laidmen, J., Zhang, W., Cacho, R., Yeates, T. O.*, Tang, Y.* “Directed Evolution and Structural Characterization of a Simvastatin Synthase.” Chem. Biol. 2009, 16, 1064-1074. Link

 

3. Biomaterials

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