个人简介

Postdoc, Merck-sponsored LSRF Fellow, Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography (with Bradley Moore) HHMI Predoctoral Fellowship and Ph.D. in Biophysical Chemistry and Macromolecular Structure, MIT (with Catherine Drennan) B.S. (Honors) in Biological Chemistry, University of Chicago

研究领域

Biological & Medicinal Chemistry; Organic Chemistry

Among the most important drug molecules in use today are organic compounds isolated from organisms such as bacteria, plants, and fungi. These molecules, known as natural products, have an incredible diversity of chemical structures and biological activities. These compounds include well-known antibiotics such as vancomycin and penicillin, and the newest generation of antibacterial agents such as daptomycin. The most important anti-cancer drugs, including taxol, doxorubicin, and vinblastine are also compounds isolated from living organisms. My research group seeks to understand how natural products are made. Living organisms synthesize complex molecules without any of the ostensible advantages of an organic chemist, such as access to high temperatures and to solvents. Critical to the assembly of these molecules are enzymes, protein catalysts, that construct these complex natural product molecules from simple and biologically available precursors. Recent technological advances in chemical biology have provided scientists with the tools to ask fundamental questions about how these molecules are made. For instance, which genes encode the necessary enzymes? What are the underlying mechanisms of these enzymes? Can we re-engineer these enzymes to catalyze the production of derivatives of the original natural products? My research team is working to isolate new biosynthetic pathways from microbes, to engineer enzymes to catalyze new reactions, and to generate natural product derivatives through combinatorial engineering and chemo-enzymatic synthesis. One of our major tools is macromolecular X-ray crystallography. We crystallize biosynthetic enzymes and determine their three-dimensional structures to provide a structural basis for understanding the catalytic mechanisms of these powerful protein machines. Overall, our research leverages a wide range of tools from chemistry and biology: structural biology, protein engineering, microbial genetics, natural product extraction, enzymology, and genomic analysis.

近期论文

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"Du, Y. - L. ; Ryan, K. S. Expansion Of Bisindole Biosynthetic Pathways By Combinatorial Construction. ACS Synthetic Biology 2015, Article ASAP.BibTex Du, Y. - L. ; Alkhalaf, L. M. ; Ryan, K. S. In Vitro Reconstitution Of Indolmycin Biosynthesis Reveals The Molecular Basis Of Oxazolinone Assembly. Proceedings of the National Academy of Sciences, United States of America 2015, 112, 2717-2722.BibTex Alkhalaf, L. M. ; Ryan, K. S. Biosynthetic Manipulation Of Tryptophan In Bacteria: Pathways And Mechanisms. Chemistry & Biology 2015, 22, 317-328.BibTex Yamanaka, K. ; Reynolds, K. A. ; Kersten, R. D. ; Ryan, K. S. ; Gonzalez, D. J. ; Nizet, V. ; Dorrestein, P. C. ; Moore, B. S. Direct Cloning And Refactoring Of A Silent Lipopeptide Biosynthetic Gene Cluster Yields The Antibiotic Taromycin A. Proceedings of the National Academy of Sciences, United States of America 2014, 111, 1957-1962.BibTex Du, Y. - L. ; Williams, D. E. ; Patrick, B. O. ; Andersen, R. J. ; Ryan, K. S. Reconstruction Of Cladoniamide Biosynthesis Reveals Non-Enzymatic Routes To Bisindole Diversity. ACS Chemical Biology 2014, 9, 2748-2754.BibTex Du, Y. - L. ; Dalisay, D. S. ; Andersen, R. J. ; Ryan, K. S. N-Carbamoylation Of 2,4-Diaminobutyrate Reroutes The Outcome In Padanamide Biosynthesis. Chemistry and Biology 2013, 20.BibTex Du, Y. - L. ; Ding, T. ; Patrick, B. O. ; Ryan, K. S. Xenocladoniamide F, Minimal Indolotryptoline From The Cladoniamide Pathway. Tetrahedron Letters 2013.BibTex Du, Y. Ling; Ding, T. ; Ryan, K. S. Biosynthetic O-Methylation Protects Cladoniamides From Self-Destruction. Organic letters 2013, 15, 2538–2541.BibTex Sydor, A. M. ; Jost, M. ; Ryan, K. S. ; Turo, K. E. ; Douglas, C. D. ; Drennan, C. L. ; Zamble, D. B. Metal Binding Properties Of Escherichia Coli Yjia, A Member Of The Metal Homeostasis-Associated Cog0523 Family Of Gtpases. Biochemistry 2013.BibTex Davies, J. ; Ryan, K. S. Introducing The Parvome: Bioactive Compounds In The Microbial World. ACS Chemical Biology 2012, 7, 252 - 259.BibTex Yamanaka, K. ; Ryan, K. S. ; Gulder, T. A. M. ; Hughes, C. C. ; Moore, B. S. Flavoenzyme-Catalyzed Atroposelective N,c-Bipyrrole Homocoupling In Marinopyrrole Biosynthesis. Journal of the American Chemical Society 2012, 134, 12434-12437.BibTex Goldman, P. ; Ryan, K. S. ; Hamill, M. J. ; Howard-Jones, A. R. ; Walsh, C. T. ; Elliott, S. J. ; Drennan, C. L. An Unusual Role For A Mobile Flavin In Stac-Like Indolocarbazole Biosynthetic Enzymes. Chemistry and Biology 2012, 19, 855-865.BibTex Ryan, K. S. Biosynthetic Gene Cluster For The Cladoniamides, Bis-Indoles With A Rearranged Scaffold. PLoS ONE 2011, 6, e23694.BibTex"