Tang, Yi


WebsiteHome URL
Division
Organic
Title
Faculty
Professor
Specialties
Organic

Contact Information

Email
Office
Boelter Hall 5531H
(310) 825-0375
Lab
Boelter Hall 5667

Research Interest

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.

Publications

2012

82. Gao, X. et al, submitted.

81. Ames, B. D., N., Chi, Smith, P., Ma, S. M., Wong, E., Wong, S., Xie, X., Li, J. W., Vederas, J. C., Tang, Y.*, Tsai, S. C.*Biosynthesis of Lovastatin: Crystal Structure and Biochemical Studies of LovC, a trans-acting Polyketide Enoyl Reductase.” Proc. Natl. Acad. Sci. U. S. A. 2012, in press.

80. Chooi, Y., Wang, P., Fan, J., Li, Y., Wu, K., Wang, P., Tang, Y.“Characterization of a Group of Fungal Aromatic Polyketide Prenyl-transferases Leads to Discovery of an Immunosuppressive Compound by Genome Mining.” J. Am. Chem. Soc. 2012, in press. Link

79. Biswas, A., Liu, Y., Fan, G.*, Tang, Y.* “Polyethylene Glycol-based Protein Nanocapsules for Functional Delivery of a Differentiation Transcription Factor” Biomaterials. 2012, in press. Link

78. Wang, P., Gao, X., Tang, Y.* “Complexity Generation during Natural Product Biosynthesis using Redox Enzymes.” Curr. Opin. Chem. Biol. 2012, in press. Link

77. 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

76. Liu, Q., Yao, F., Chooi, Y., Kang, Q., Xu, W., Li, Y., Shao, Y., Shi, Y., Deng, Z., Tang, Y.*., You, D.* “Elucidation of Piericidin A1 Biosynthetic Locus Revealed an Thioesterase-dependent Mechanism of α-Pyridone Ring Formation.” Chem. Biol. 2012, 19, 243-253. Link

75. Winter, J. M., Tang, Y.* “Synthetic Biological Approaches to Natural Product Biosynthesis.” Curr. Opin. Biotech. 2012, in press. Link

74. Zabala, A. O., Cacho, R., Tang, Y.* “Protein Engineering Towards Natural Product Synthesis and Diversification.” J. Ind. Microb. Biotechnol. 2012, 39, 227-241. (Invited Review) Link

2011

73. Pickens, L. B., Sawaya, M. R., Pashkov, I., Rasool, H., Yeates, T. O., Tang, Y.* “Structural and Biochemical Characterizations of the GDSL Salicylyl-Acyltranferase SsfX3 from a Tetracycline Biosynthetic Pathway.” J. Biol. Chem. 2011, 286, 41539-41553 (selected as Paper of the Week). Link

72. Qiao, K. Chooi, Y., Tang, Y.* “Identification and Engineering of the Cytochalasin E Gene Cluster from Aspergillus clavatus.” Metab. Eng. 2011, 13, 723-732. Link

71. Li, Y., Chooi, Y., Sheng, Y., Valentine, J. S., Tang, Y.* “Comparative Characterization of Fungal Anthracenone and Naphthacenedione Biosynthetic Pathways Reveals an alpha-Hydroxylation-Dependent Claisen-Like Cyclization Catalyzed by a Dimanganese Thioesterase.” J. Am. Chem. Soc. 2011, 133, 15773-15785. Link

70. Ames, B. D., Haynes, S. W., Gao, X., Evans, B. S., Kelleher, N. L., Tang, Y., Walsh, C. T.*, “Complexity Generation in Fungal Peptidyl Alkaloid Biosynthesis: Oxidation of Fumiquinazoline A to the Heptacyclic Hemiaminal Fumiquinazoline C by the Flavoenzyme Af12070 from Aspergillus fumigatus.” Biochemistry 2011, 50, 8756-8769. Link

69. Ames, B. D., Lee, M., Moody, C., Zhang, W., Tang, Y., Tsai, S. C.* “Structural and Biochemical Characterization of ZhuI Aromatase/Cyclase from the R1128 Polyketide Pathway.” Biochemistry 2011, 50, 8392–8406. Link

68. Wang, P., Gao., X., Deng, Z., Tang, Y.* “Genetic Characterization of Enzymes Involved in the Priming Steps of Oxytetracycline Biosynthesis in Streptomyces rimosus.” Microbiology, 2011, 157, 2401-2409. Link

67. Haynes, S. W., Ames, B. D., Gao, X., Tang, Y., Walsh, C. T.* “Unraveling Terminal C-Domain-Mediated Condensation in Fungal Biosynthesis of Imidazoindolone Metabolites.” Biochemistry 2011, 50, 5668-5679. Link

66. Gu, Z., Biswas, A., Zhao, M., Tang, Y.* “Nanocarriers for Protein Intracellular Delivery.” Chem. Soc. Rev. 2011, 40, 3638-3655. Link

65. 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

64. Joo, K., Fang, Y., Liu, Y., Xiao, L., Gu, Z., Tai, A., Lee, C., Tang, Y., Wang, P.* “Enhanced Real-Time Monitoring of Adeno-Associated Virus Trafficking by Virus-Quantum Dot Conjugates.” ACS Nano 2011, 5, 3523-3535. Link

 

63. Gu, Z., Zhao, M., Sheng, Y., Bentolila, L. A. Tang, Y.* “Detection of Mercury Ion by Infrared-Fluorescent Protein and Its Hydrogel-Based Paper Assay.” Anal. Chem. 2011, 83, 2324-2329. Link

 

62. Qiao, K., Zhou, H., Xu, W., Zhang, W., Garg, N., Tang, Y.* “A Fungal Nonribosomal Peptide Synthetase Module that can Synthesize Thiopyrazines.” Org. Lett. 2011, 13, 1758-1761. Link

 

61. Gao, X., Chooi, Y., Ames, B. D., Wang, P., Walsh, C. T., Tang, Y.* “Fungal Quinazoline Alkaloid Biosynthesis: Genetic and Biochemical Investigation of the Tryptoquialanine Pathway in Penicillium aethiopicum.” J. Am. Chem. Soc. 2011, 133, 2729-2741. Link Highlighted by Nature Chem Biol.

 

60. Biswas, A., Joo, K., Zhao, M., Fan, G., Wang, P., Zhen, G., Tang, Y.* “Endoprotease-Mediated Intracellular Protein Delivery using Nanocapsules.”ACS Nano 2011, 5, 1385-1394. Link

59. Pickens, L., Tang, Y.*, Chooi, Y. H. “Metabolic Engineering for the Production of Natural Products” Annu. Rev. Chem. Bio. Eng. 2011, in press. (Invited Review) Link

58. Meehan, M. J.; Xie, X.; Zhao, X.; Xu, W.; Tang, Y.*; Dorrestein, P. C.* “FT-ICR-MS characterization of intermediates in the biosynthesis of the α-methylbutyrate side chain of lovastatin by the 277 kDa polyketide synthase LovF.” Biochemistry 2011, 50, 287–299. Link

2010

57. Zhou, H., Qiao, K., Gao, Z., Vederas, J. C.*, Tang, Y.* “Insights into Radicicol Biosynthesis via Heterologous Synthesis of Advanced Intermediates and Analogs.” J. Biol. Chem. 2010, 285, 41412-4121. Link

56. Xu, W., Cai, X., Jung, M. E., Tang, Y.* “Analysis of Intact and Dissected Fungal Polyketide Synthase-Nonribosomal Peptide Synthetase in vitro and in Saccharomyces cerevisiaeJ. Am. Chem. Soc. 2010, 132, 13604-13607. Link

55. Gao, X., Wang, P., Tang, Y.*, “Engineered polyketides biosynthesis and biocatalysis in Escherichia coli.” Appl. Microbiol. Biotechnol. 2010, 88, 1233-1242. (Invited Minireview) Link

54. Chooi, Y. H., Tang, Y.*, “Adding the Lipo to Lipopeptides: Do More with Less.” Chem. Biol. 2010, 17, 791-793. Link

53. Gu, Z., Biswas, A., Joo, K., Hu, B., Wang, P. and Tang, Y.*, “Probing Protease Activity with a Single Fluorescent Protein Nanobeacon.” Chem. Commun. 2010, 46, 6467-6469. Link

52. Pickens, L., Tang, Y.*, “Oxytetracycline Biosynthesis.” J. Biol. Chem. 2010, 285, 27509-27515 (Invited minireview). Link

51. Chooi, Y. H., Cacho, R., Tang, Y.*, “Identification of the Viridicatumtoxin and Griseofulvin Gene Clusters from Penicillium aethiopicum.” Chem. Biol. 2010, 17, 483-494. Link

50. Li, Y., Xu, W., Tang, Y.*, “Classification, Prediction and Verification of the Regioselectivity of Fungal Polyketide Synthase Product Template Domains.” J. Biol. Chem. 2010, 285, 22762-22771. Link Highlighted by Nature Chem Biol.

49. Gu, Z., Tang, Y.*, “Enzyme-Assisted Photolithography for Spatial Functionalization of Hydrogels.” Lab on Chip 2010, 10, 1946-1951. (FRONT COVER) Link

48. Zhou, H., Li, Y., Tang, Y.*, “Cyclization of Aromatic Polyketides from Bacteria and Fungi.” Nat. Prod. Rep. 2010, 27, 839-868. Link

47. Zhou, H., Qiao, K., Gao, Z.; Meehan, M. J., Li, J., Dorrestein, P. C., Vederas, J. C.*, Tang, Y.*, “Enzymatic Synthesis of Resorcylic Acid Lactones by Cooperation of Fungal Iterative Polyketide Synthases Involved in Hypothemycin Biosynthesis.” J. Am. Chem. Soc. 2010, 132, 4530–4531. Link

46. Yan, M, Du, J. J. Gu, Z., Liang, M., Hu, Y., Zhang, W., Segura, T., Liu, Z., Tang, Y. Lu, Y*. “A Novel Intracellular Protein Delivery Platform Based on Single-Protein Nanocapsules” Nat. Nano., 2010, 5.

2009

45. Gu, Z., Yan, M., Hu, B., Joo, K., Biswas, A., Lu, Y.*, Wang, P.*, Tang, Y.* “Protein Nanocapsules Weaved by an Enzymatically Degradable Polymer Network.” Nano. Lett. 2009, 9, 4533-4538. Link

44. 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

43. Pickens, L. B., Kim, W., Wang, P., Zhou, H., Watanabe, K., Gomi, S., Tang, Y.* “Biochemical Analysis of the Biosynthetic Pathway of an Anticancer Tetracycline SF2575.” J. Am. Chem. Soc. 2009, 131, 17677–17689. Link

42. 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

41. Wang, M., Zhou, H., Wirz, M., Tang, Y., Boddy, C. N.* “A Versatile Thioesterase from an Iterative Fungal Polyketide Synthase.” Biochemistry 2009, 48, 6288-6290. Link

40. Xie, X., Meehan, M. J. Xu, W., Dorrestein, P. C., Tang, Y.* “Acyltransferase Mediated Polyketide Release From Fungal Megasynthase.” J. Am. Chem. Soc. 2009, 131, 8388-8389. Link

39. Wang, P., Zhang, W., Zhan, J., Tang, Y.* “Identification of OxyE as an Ancillary Oxygenase During Tetracycline Biosynthesis.” ChemBioChem, 2009, 10, 1554-1550. Link

38. Zhan, J., Qiao, K., Tang, Y.* “Investigation of Post-PKS Tailoring Modifications in Pradimicin Biosynthesis.” ChemBioChem, 2009, 10, 1447-1452. Link

37. Ma, S. M., Pickens, L. B., Tang, Y.* “Antibiotics, Polyketides.” Encyclopedia of Industrial Biotechnology, 2009, in press.

36. Zhang, W., Tang, Y.* “In vitro Analysis of Type II Polyketides.” Methods in Enzymology Volume: Complex Enzymes in Microbial Natural Product Biosynthesis. 2009, 459, 367-393. Link

35. Pickens, L. B., Tang, Y. * “Decoding and Engineering Tetracycline Biosynthesis.” Metab. Eng. 2009, 11, 69-75. (Cover article). Link

34. Xie, X., Pashkov, I., Xue, G., Guerrero, J., Yeates, T., Tang, Y.* “Rational Improvement of Simvastatin Synthase Solubility in Escherichia coli Leads to Higher Whole-cell Biocatalytic Activity.” Biotechnol. Bioeng. 2009, 102, 20-28. Link

2008

33. Zhang, W., Li, Y., Tang, Y. “Engineered Biosynthesis of Bacterial Aromatic Polyketides in Escherichia coli.” Proc. Natl. Acad. Sci. USA., 2008, 105, 20683-20685. Link

32. Zhou, H., Xie, X., Tang, Y.* “Engineering Natural Products Using Combinatorial Biosynthesis and Biocatalysis.” Curr. Opin. Biotechnol., 2008, 19, 590-596. Link

31. Zhan, J., Watanabe, K., Tang, Y.* “Synergistic Actions of Monooxygenase and Cyclases in Aromatic Polyketide Biosynthesis.” ChembioChem 2008, 9, 1710 – 1715. Link

30. Zhang, W., Watanabe, K., Cai, X., Jung, M. E., Tang, Y.*, Zhan, J.* “Identifying the Minimal Enzymes Required for Anhydrotetracycline Biosynthesis.” J. Am. Chem. Soc. 2008, 130, 6068-6069. Link

29. Zhou, H., Zhan, J., Watanabe, K., Xie, X., Tang, Y.* “A Polyketide Macrolactone Synthase from the Filamentous Fungus Gibberella zeae.” Proc. Natl. Acad. Sci. USA, 2008, 105, 6249-6254. Link

28. Ames, B., Korman, T., Zhang, W., Smith, P., Vi, T., Tang, Y., Tsai, S-C. “Crystal Structure and Functional Analysis of Tetracenomycin ARO/CYC: Implications for Cyclization Specificity of Aromatic Polyketides.” Proc. Natl. Acad. Sci. USA, 2008, 105, 5349-5354. Link

27. Ma, S. M., Zhan, J., Xie, X., Watanabe, K., Tang, Y.*, Zhang, W. “Redirecting the Cyclization Steps of Fungal Polyketide Synthase.” J. Am. Chem. Soc. 2008, 130, 38-39. Link

26. Zhang, W., Tang, Y.* “Combinatorial Biosynthesis of Natural Products” J. Med Chem. 2008, 51, 2629-2633. Link

2007

25. Ma, S. M., Zhan, J., Watanabe, K., Xie, X., Zhang, W., Wang, C. C., Tang, Y.* “Enzymatic Synthesis of Aromatic Polyketides using PKS4 from Gibberella fujikuroi.” J. Am. Chem. Soc. 2007, 129, 10642-10643. Link

24. Zhang, W.; Wilke, B. I.; Zhan, J.; Watanabe, K.; Boddy, C. N.*; Tang, Y.* “A New Mechanism for Benzopyrone Formation in Aromatic Polyketide Biosynthesis.” J. Am. Chem. Soc. 2007, 129, 9304-9305. Link.

23. Zhang, W., Watanabe. K., Wang, C. C. C., Tang, Y.* “Investigation of Early Tailoring Reactions in the Oxytetracycline Biosynthetic Pathway.” J. Biol. Chem. 2007, 282, 25717-25725. Link.

22. Xie, X., Wong, W. W., Tang, Y.* “Improving Simvastatin Bioconversion in Escherichia coli by Deletion of bioH.” Metab. Eng. 2007, 9, 379-386. Link

21. Ma, S. M., Tang, Y.* “Biochemical Characterization of the Minimal Polyketide Synthase Domains in the Lovastatin Nonaketide Synthase LovB.” FEBS J. 2007, 274, 2854–2864. Link

20. Xie, X., Tang, Y.* “Efficient Synthesis of Simvastatin Using Whole-Cell Biocatalysis.” Appl. Environ. Microb. 2007, 73, 2054-2060. Link

2006

19. Zhang, W., Watanabe, K., Wang, C. C. C., Tang, Y.* “Heterologous Biosynthesis of Amidated Polyketides with Novel Cyclization Regioselectivity from Oxytetracycline Polyketide Synthase” J. Nat. Prod. 2006, 69, 1633-1636. Link

18. Xie, X., Watanabe, K., Wojcicki, W. A., Wang, C. C. C., Tang, Y.* “Biosynthesis of lovastatin analogs with a broadly specific acyltransferase.” Chem. Biol. 2006, 13, 1161-1169. Link

17. Zhang, W., Ames, B., Tsai, S-C., Tang, Y.*, "Tetracycline Biosynthesis: Sequencing of the Oxytetracycline Gene Cluster and Reconstitution of the Malonamyl-Specific Initiation module." Appl. Environ. Microb. 2006, 72, 2573-2580. link

 

Publication from Postdoctoral Work

16. Tang, Y. Lee, H.Y., Tang, Y., Kim, C-Y., Mathews, I. and Khosla, C. “Structural and Functional Studies on SCO1815: A -Ketoacyl-Acyl Carrier Protein Reductase from Streptomyces coelicolor A3(2).” Biochemistry, 2006, 45, 14085-14093.

15. Lee. T. S.*, Khosla, C., Tang, Y.* "Orthogonal Protein Interactions in Spore Pigment Producing and Antibiotic Producing Type II Polyketide Synthases." J. Antibiotics, 2005, 58, 664-667.

14. Lee. T. S.*, Khosla, C., Tang, Y.* "Engineered Biosynthesis of Aklanonic Acid Analogs." J. Am. Chem. Soc., 2005, 127, 12254-12262.

13. Khosla, C., Tang, Y., "Chemistry. A new route to designer antibiotics." Science 2005, 308, 367-368.

12. Tang, Y., Koppisch, A., Khosla, C. "The Acyltransferase Homolog Found in Initiation Modules of Type II PKS is an Acetyl-ACP Thiolase that Suppresses Acetate-Priming of the KS-CLF." Biochemistry 2004, 43, 9546-9555.

11. Tang, Y., Lee, T. S., Lee, H. Y., Khosla, C. "Exploring the Biosynthetic Potential of Bimodular Aromatic Polyketide Synthases." Tetrahedron, 2004, 7659-7671.

10. Kumar, P.*, Khosla, C., Tang, Y.* "Manipulation and Analysis of Polyketide Synthases." Methods in Enzymology Volume 388: Protein Engineering 2004, 269-293.

9. Tang, Y., Lee, T. S., Khosla, C. "Engineered Biosynthesis of Regioselectively Modified Aromatic Polyketides Using Bimodular Polyketide Synthases." PLoS Biol. 2004, 2, 227-237.

8. Tang, Y., Tsai, S. C., Khosla, C. "Polyketide Chain Length Control by Chain Length Factor." J. Am. Chem. Soc. 2003, 125, 12708-12709.

7. Tang, Y., Lee, T. S., Kobayashi, S., Khosla, C. "Ketosynthases in the Initiation and Elongation Modules of Aromatic Polyketide Synthases Have Orthogonal Acyl-Carrier Protein Specificity." Biochemistry 2003, 42, 6588-6595.

 

Publication from Graduate Work

6. Cirino, P.C , Tang, Y., Takahashi, K., Tirrell, D. A., Arnold, F. H. "Global Incorporation of Norleucine in Place of Methionine in Cytochrome P450 BM-3 Heme Domain Increases Peroxygenase Activity." Biotechnol Bioeng. 2003, 20, 729-734.

5. Wang, P., Tang, Y., Tirrell, D. A., "Incorporation of Trifluoroisoleucine into Proteins In Vivo." J. Am. Chem. Soc. 2003, 125, 6900-6906.

4. Tang, Y., Tirrell, D. A. "Attenuation of Leucyl-tRNA Synthetase Proofreading Activity in Escherichia coli Allows Introduction of An Array of Unnatural Amino Acids in vivo." Biochemistry 2002, 41, 10635-10645.

3. Tang, Y., Tirrell, D. A. "Biosynthesis of Highly Stable Coiled-coils Containing Hexafluoroleucine Using an Engineered Bacterial Host." J. Am. Chem. Soc. 2001, 123, 11089-11090.

2. Tang, Y., Ghirlanda, G., Petka, W. A., Nakajima, T., W. A., DeGrado, W. F., Tirrell, D. A. "Fluorinated Coiled-coils Prepared in vivo Display Enhanced Thermal and Chemical Stability." Angew. Chem. Int. Ed. 2001, 40, 1494-1497.

1. Tang, Y., Ghirlanda, G., Vaidehi, N., Kua, J., Mainz, D. T., Goddard, W. A., DeGrado, W. F., Tirrell, D. A. "Stabilization of Leucine Zipper Coiled-coils using Trifluoroleucine." Biochemistry 2001, 40, 2790-2796.

 

Book Chapters

 

6. Gu, Z.*, Tang, Y., Chen, Y., “Fabrication of Biomolecular Nanopatterns.” In Advances in Nanotechnology Volume III. eds Bartul, Z. and Jérôme Trenor, J.; NOVA scientific publisher, 2010.

5. Xie, X., Qiao, K. J., Tang, Y.* “Metabolic Engineering of Natural Product Biosynthesis.” In Bioactive Compounds from Natural Sources, Second Edition: Natural Products as Lead Compounds in Drug Discovery. ed Tringlai, C., Taylor and Francis Group, 2010.

4. Zhang, W., Ferreira, J. P., Tang, Y. "Regulation of Secondary Metabolism Biosynthesis." In: Smolke, C.D., ed. Handbook for Metabolic Pathway Engineering. CRC Press. 2009 in press.

3. Tang, Y.; Ma, S.M; Wojcicki, W. A. "Applications of Metabolic Engineering for Natural Drug Discovery." In: Smolke, C.D., ed. Handbook for Metabolic Pathway Engineering. CRC Press. 2009 in press.

2. Zhang, W., Tang, Y., "Engineering Starter Units in Aromatic Polyketides." In ACS Volume Based on Polyketides: Biosynthesis, Biological Activity and Genetic Engineering. eds S. R. Baerson; American Chemical Society, 2006.

1. Tang, Y., Khosla, C., "Diversity from Mother Nature: natural and unnatural products." In Exploiting Chemical Diversity for Drug Discovery, eds P. Bartlett and M. Entzeroth; Royal Society of Chemistry, 2006. Link