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Clay C. Wang

Associate Professor of Pharmacology, Pharmaceutical Sciences, and Chemistry
Chemical Biology

NIH Postdoctoral Fellow 2001-2003 Stanford University
Ph.D., 2001, California Institute of Technology
A.B., 1996 Harvard University
Office: PSC 716
Phone: (323) 442-1670
Fax:
Email: clayw@usc.edu
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Research Focus

 
The primary focus of my lab is to use an interdisciplinary approach to study natural product biosynthesis. Specifically my lab has been studying two aspects of natural product chemistry 1) discovery of natural products and their biosynthesis pathways in fungal genomes and 2) development of a heterologous host for natural product production. Both of these rely on recent advances in genome sequencing of natural product producing organisms. My research seeks to leverage this information into drug discovery that can ultimately benefit human health.

A. Genomic mining of natural products and their biosynthesis pathways in fungi.

This research program involves studying fungal secondary metabolites, their regulation and their biosynthesis pathways. An outstanding issue in the field is that genome sequencing of natural product producing organisms has revealed that each organism has the potential to synthesize a surprisingly large range of natural products, many of which are currently unknown. My lab is using advances in fungal genetics to decipher the products of these cryptic pathways.

B. Heterologous host production of natural products

The primary goal of this project is to develop a "universal" heterologous expression system that would enable the convenient, high-yield expression of a wide range of natural products from a variety of natural sources. This is a particularly attractive approach because using one "universal" system then would eliminate the need to develop a different genetic system for each individual organism.

Selected publications

 

* denotes corresponding author

1. Sanchez, J. F., Chiang, Y., Szewczyk, E., Davidson, A. D., Ahuja, M., Oakley, C. E., Bok, J. W., Keller N. P., Oakley B. R., & Wang C. C. C.* , Molecular genetic analysis of the orsellinic acid/F9775 gene cluster of Aspergillus nidulans. Mol. BioSyst. 2009; accepted.
2. Chiang, Y., Lee, K., Sanchez J. F., Keller, N. P.*, & Wang, C. C. C.*, Unlocking Fungal Cryptic Natural Products. Nat. Prod. Comm. 2009; 5: 1505-1510.
3. Watanabe, K., Hotta, K., Praseuth, A., Searcey, M., Wang, C.C.C., Oguri, H., Oikawa, H., Rationally engineered total biosynthesis of a synthetic analogue of a natural quinomycin depsipeptide in Escherichia coli. Chembiochem 2009; 10: 1965-1968.
4. Li, A., Lee, M. B. Lin, H., Wang, C. C. C., Yen, Y., Chen B., David, C., Ann, D., Suppression of Non-Homologous End Joining Repair by Overexpression of HMGA2. Cancer Research 2009; 69: 5699-5706.
5. Watanabe, K., Hotta, K., Nakaya, A., Praseuth, A., Wang, C.C.C., Inada, D., Takahashi, K., Fukushi E., Oguri, H., Oikawa, H., Escherichia coli Allows Efficient Modular Incorporation of Newly Isolated Quinomycin Biosynthetic Enzyme into Echinomycin Biosynthetic Pathway for Rational Design and Synthesis of Potent Antibiotic Unnatural Natural Product. J. Am. Chem. Soc. 2009; 131: 9347-9353.
6. Bok, J. W., Chiang, Y., Szewczyk, E., Davidson, A. D., Sanchez, J. F., Lo, H. C. Watanabe, K., Oakley B. R., Wang C. C. C.*, & Keller N. P.* Chromatin-level regulation of cryptic biosynthetic gene clusters in Aspergillus nidulans. Nature Chemical Biology 2009; 5: 462-464. Highlighted in Faculty of 1000.
7. Chiang, Y., Szewczyk, E., Davidson, A. D., Keller, N. P., Oakley, B. R.*, & Wang C. C. C.* Discovery of a polyketide, asperfuranone, and its biosynthetic gene cluster in Aspergillus nidulans using a genome mining approach. J. Am. Chem. Soc. 2009; 131: 2965-2970.
8. Szewczyk, E., Chiang, Y., Oakley, E., Davidson, A. D., Wang C. C. C.*, & Oakley B. R.* SUMO regulation of secondary metabolite production in Aspergillus nidulans: Identification of the asperthecin gene cluster. Appl. Environ. Microbiol. 2008; 74: 7607-7612.
9. Sanchez, J.F., Chiang Y., & Wang C. C. C.* Diversity of Polyketide Synthases Found in the Aspergillus and Streptomyces Genomes. Mol. Pharm. 2008; 5: 226-233.
10. Praseuth, A., Wang C. C. C.*, Watanabe, K.* , Hotta, K., Oguri, H., & Oikawa, H., Complete Sequence of Biosynthetic Gene Cluster Responsible for Producing Triostin A and Evaluation of Quinomycin-Type Antibiotics from Streptomyces triostinicus. Biotechnol. Prog. 2008; 24: 1226-1231.
11. Wang C. C. C., Chiang, Y., Kuo, P. L., Chang, J. K., & Hsu, Y. L. Norsolorinic acid inhibits proliferation of T24 human bladder cancer cells via arresting the cell cycle at G0/G1 phase and inducing Fas/mFas ligand mediated apoptotic pathway. Clin. Exp. Pharmacol. Physiol. 2008; 35: 1301-1308.
12. Chiang, Y., Szewczyk, E., Nayak, T., Sanchez, J. F., Lo, H., Simityan, H., Kuo, E., Praseuth, A., Watanabe, K., Oakley, B. R.*, & Wang C. C. C.* Discovery of the Emericellamide gene cluster: An efficient gene targeting system for the genomic mining of natural products in Aspergillus nidulans. Chem. Biol. 2008; 15: 527-532.
13. Wang C. C. C., Chiang, Y., Kuo, P. L., Chang, J. K., & Hsu, Y. L. Norsolorinic Acid from Aspergillus nidulans Inhibits the Proliferation of Human Breast Adenocarcinoma MCF-7 Cells via Fas-Mediated Pathway. Basic Clin. Pharmacol. Toxicol. 2008; 102: 491-497.
14. Wang C. C. C., Chiang, Y., Sung, S. C., Hsu, Y. L., Chang, J. K., & Kuo, P. L. Plumbagin induces cell cycle arrest and apoptosis through reactive oxygen species/c-Jun N-terminal kinase pathways in human melanoma A375.S2 cells. Cancer Lett. 2008; 259: 82-89.
15. Praseuth, A., Praseuth, M. B., Oguri, H., Oikawa, H., Watanabe, K., & Wang C. C. C.* Improved Production of Triostin A in Engineered Escherichia coli with Furnished Quinoxaline Chromophore by Design of Experiments in Small-Scale Culture. Biotechnol. Prog. 2008; 24: 134-139.
16. 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.
17. Ma, S. M., Zhan, J., Watanabe, K., Xie, X., Zhang, W., Wang C. C. C., & Tang, Y. Enzymatic Synthesis of Aromatic Polyketides Using PKS4 from Gibberalla fujikuroi. J. Am. Chem. Soc. 2007; 129: 10642-10643.
18. Marques, M., Citron, D., & Wang C. C. C.* Development of Tyrocidine A Analogues with Improved Antibacterial Activity. Bioorg. Med. Chem. 2007; 15: 6667-6677.
19. Hsu, C. F., Phillip, J. W., Trauger, J. W., Farkas, M. E., Belitsky, J. M., Heckel, A., Olenyuk, B. Z., Puckett, J. W., Wang C. C. C. & Dervan, P. B. DNA Completion of a programmable DNA-binding small molecule library. Tetrahedron 2007; 63: 6146-6151.
20. Watanabe, K., Praseuth, A., & Wang C. C. C.* A comprehensive and engaging overview of the type III family of polyketide synthase. Curr. Opin. Chem. Biol. 2007; 11: 279-286.
21. 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; 11: 1633-1636.
22.Xie, X., Watanabe, K., Wladyslaw A., Wang C. C. C., & Tang Y. Lovastatin Acyltransferase with Broad Specifcity. Chem. Biol. 2006; 13: 1161-1169.
23.Watanabe, K., Hotta, K., Praseuth, A. P., Koketsu K., Migita A., Boddy C. N., Wang C. C. C., Oguri H., & Oikawa H. Total biosynthesis of antitumor nonribosomal peptides in Escherichia coli. Nature Chemical Biology 2006; 2: 398-400.
24.Watanabe, K., Wang C. C. C., Boddy, C. N., Cane, D. E. & Khosla, C. Understanding Substrate Specificity of Polyketide Synthase Modules by Generating Hybrid Multimodular Synthases. J. Biol. Chem. 2003; 278: 42020–42026.
25.Pfeifer, B. A., Wang C. C. C., Walsh, C. T. & Khosla, C. Biosynthesis of Yersiniabactin, a Complex Polyketide/Nonribosomal Peptide, Using Escherichia coli as a Heterologous Host. Appl. Environ. Microbiol. 2003; 69: 6698–6702.
26.Wang C. C. C. & Dervan, P. B. Sequence Specific Recruitment of Topoisomerase I by DNA Binding Polyamide-Camptothecin Conjugates. J. Am. Chem. Soc. 2001; 123: 8657–8661.
27.Wang C. C. C., Ellervik, U., & Dervan, P. B. Expanding the Recognition of the Minor Groove of DNA by Incorporation of β-Alanine in Hairpin Polyamides. Bioorg. Med. Chem. 2001; 9: 653–657.
28.Ellervik, U., Wang C. C. C., & Dervan, P. B. Hydroxybenzamide/Pyrrole Pair Distinguishes T-A from A-T Base Pairs in the Minor Groove of DNA. J. Am. Chem. Soc. 2000; 122: 9354–9360.
29.Simanek, E. E., Wang C. C. C., Whitesides, G. M., McBridge, M. T., & Palmore, G. T. R. Benzimidazolene-2-thiones: A New Class of Molecules for the Engineering of Molecular Tapes in the Organic Solid State. Chem Mater. 1997; 9: 1954–1961.
30.Simanek, E. E., Isaacs, X. H., Li, X. H., Wang C. C. C., & Whitesides, G. M. Self-assembly of Zinc Porphyrins Around the Periphery of Hydrogen-bonded Aggregates that Bear Imidazole Groups. J. Org. Chem. 1997; 62: 8994–9000.
 

Chemistry Dept., USC College of Letters, Arts & Sciences