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Katherine Ryan


Research and Teaching Interests


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 us 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.

To find out more or to inquire about available positions, please email ksryan at chem.ubc.ca.  




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Curriculum Vitae

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



Daniel-Ivad, P. ; Ryan, K. S. Structure Of Methyltransferase Redm That Forms The Dimethylpyrrolinium Of The Bisindole Reductasporine. Journal of Biological Chemistry 2024, https://doi.org/10.1016/j.jbc.2023.105520.
Daniel-Ivad, P. ; Ryan, K. S. An Imine Reductase That Captures Reactive Intermediates In The Biosynthesis Of The Indolocarbazole Reductasporine. Journal of Biological Chemistry 2024, https://doi.org/10.1016/j.jbc.2024.105642.


Wang, M. ; Ryan, K. S. Reductases Produce Nitric Oxide In An Alternative Pathway To Form The Diazeniumdiolate Group Of L-Alanosine. Journal of the American Chemical Society 2023, 145, 16718-16725.
Higgins, M. A. ; Shi, X. ; Soler, J. ; Harland, J. B. ; Parkkila, T. ; Lehnert, N. ; Garcia-Borràs, M. ; Du, Y. - L. ; Ryan, K. S. Structural And Mechanistic Views Of Enzymatic, Heme-Dependent Nitrogen-Nitrogen Bond Formation. bioRxiv 2023, https://doi.org/10.1101/2023.12.15.571702.


He, H. - Y. ; Niikura, H. ; Du, Y. - L. ; Ryan, K. S. Synthetic And Biosynthetic Routes To Nitrogen–Nitrogen Bonds. Chem. Soc. Rev. 2022, 51, 2991-3046.
Morgan, K. D. ; Williams, D. E. ; Ryan, K. S. ; Andersen, R. J. Dentigerumycin F And G: Dynamic Structures Retrieved Through A Genome-Mining/nitrogen-Nmr Methodology. Tetrahedron Letters 2022, 94, 153688.
Williams, D. E. ; Morgan, K. D. ; Dalisay, D. S. ; Matainaho, T. ; Perrachon, E. ; Viller, N. ; Delcroix, M. ; Gauchot, J. ; Niikura, H. ; Patrick, B. O. ; Ryan, K. S. ; Andersen, R. J. Natural Products Produced In Culture By Biosynthetically Talented Salinispora Arenicola Strains Isolated From Northeastern And South Pacific Marine Sediments. Molecules 2022, 27, 3569.
Wei, Z. - W. ; Niikura, H. ; Morgan, K. D. ; Vacariu, C. M. ; Andersen, R. J. ; Ryan, K. S. Free Piperazic Acid As A Precursor To Nonribosomal Peptides. J. Am. Chem. Soc. 2022, ASAP.


Hoffarth, E. R. ; Kong, S. ; He, H. - Y. ; Ryan, K. S. An Engineered Biosynthetic-Synthetic Platform For Production Of Halogenated Indolmycin Antibiotics. Chemical Science 2021, 12.
Bell, E. L. ; Finnigan, W. ; France, S. P. ; Green, A. P. ; Hayes, M. A. ; Hepworth, L. J. ; Lovelock, S. L. ; Niikura, H. ; Osuna, S. ; Romero, E. ; Ryan, K. S. ; Turner, Nj.; Flitsch, S. L. Biocatalysis. Nature Reviews Methods Primers 2021, 1.
Hoffarth, E. R. ; K. Haatveit, C. ; Kuatsjah, E. ; MacNeil, G. A. ; Saryoa, S. ; Walsby, C. J. ; Eltis, L. D. ; Houk, K. N. ; Garcia-Borràs, M. ; Ryan, K. S. A Shared Mechanistic Pathway For Pyridoxal Phosphate-Dependent Arginine Oxidases. PNAS 2021, 118, e2012591118.
He, H. - Y. ; Ryan, K. S. Glycine-Derived Nitronates Bifurcate To O-Methylation Or Denitrification In Bacteria. Nature Chemistry 2021, 13, 599-606.
Higgins, M. A. ; Tegl, G. ; Macdonald, S. S. ; Arnal, G. ; Brumer, H. ; Withers, S. G. ; Ryan, K. S. N-Glycan Degradation Pathways In Gut- And Soil-Dwelling Actinobacteria Share Common Core Genes. ACS Chem. Biol. 2021, 16.


Wang, M. ; Niikura, H. ; He, H. - Y. ; Daniel-Ivad, P. ; Ryan, K. S. Biosynthesis Of The Nitrogen‐Nitrogen Bond‐Containing L‐Alanosine. Angewandte Chemie 2020, 59, 3881-3885.
Hedges, J. B. ; Ryan, K. S. Biosynthetic Pathways To Nonproteinogenic Alpha-Amino Acids. Chemistry Reviews 2020, 120, 3161-3209.
Zhao, G. ; Yao, S. ; Rothchild, K. W. ; Liu, T. ; Liu, Y. ; Lian, J. ; He, H. - Y. ; Ryan, K. S. ; Du, Y. - L. The Biosynthetic Gene Cluster Of Pyrazomycin-A C-Nucleoside Antibiotic With A Rare Pyrazole Moiety. ChemBioChem 2020, 21, 644-649.
Hoffarth, E. R. ; Rothchild, K. W. ; Ryan, K. S. Emergence Of Oxygen- And Pyridoxal Phosphate-Dependent Reactions. FEBS J 2020, 287, 1403-1428.
Morgan, K. D. ; Williams, D. E. ; Patrick, B. O. ; Remigy, M. ; Banuelos, C. A. ; Sadar, M. D. ; Ryan, K. S. ; Andersen, R. J. Incarnatapeptins A And B, Nonribosomal Peptides Discovered Using Genome Mining And 1H/15N Hsqc-Tocsy. Org. Lett 2020, 22, 4053-4057.
Beskrovnaya, P. ; Melnyk, R. A. ; Liu, Z. ; Higgins, M. A. ; Song, Y. ; Ryan, K. S. ; Haney, C. H. Cite Share Comparative Genomics Identified A Genetic Locus In Plant-Associated Pseudomonas Spp. That Is Necessary For Induced Systemic Susceptibility. mBio 2020, 11, e00575-20.
Kudo, Y. ; Awakawa, T. ; Du, Y. - L. ; Jordan, P. A. ; Creamer, K. E. ; Jensen, P. R. ; Linington, R. G. ; Ryan, K. S. ; Moore, B. S. Expansion Of Gamma-Butyrolactone Signaling Molecule Biosynthesis To Phosphotriester Natural Products. ACS Chemical Biology 2020, 15, 3253-3261.
Kuzuyama, T. ; Ryan, K. S. Mechanistic Biology In The Biosynthesis Of Specialized Metabolites. Current Opinion in Chemical Biology 2020, 59, A1-A3.


Du, Y. - L. ; Ryan, K. S. Pyridoxal Phosphate-Dependent Reactions In The Biosynthesis Of Natural Products. Natural Product Reports 2019, 36, 430-457.
He, H. Y. ; Henderson, A. C. ; Du, Y. L. ; Ryan, K. S. A Two-Enzyme Pathway Links L-Arginine To Nitric Oxide In N-Nitroso Biosynthesis. Journal of the American Chemical Society 2019, 141, 4026-4033.
Morgan, K. D. ; Andersen, R. J. ; Ryan, K. S. Piperazic Acid-Containing Natural Products: Structures And Biosynthesis. Natural Product Reports 2019, 36, 1628-1653.
Hedges, J. B. ; Ryan, K. S. In Vitro Reconstitution Of The Biosynthetic Pathway To The Nitroimidazole Antibiotic Azomycin. Angewandte Chemie 2019, 58, 11647-11651.
Guo, J. ; Higgins, M. A. ; Daniel-Ivad, P. ; Ryan, K. S. An Asymmetric Reductase That Intercepts Acyclic Imino Acids Produced In Situ By A Partner Oxidase. Journal of the American Chemical Society 2019, 141, 12258-12267.
Du, Y. Ling; Higgins, M. A. ; Zhao, G. ; Ryan, K. S. Convergent Biosynthetic Transformations To A Bacterial Specialized Metabolite. Nature Chemical Biology 2019, 15, 1043-1048.


Hedges, J. B. ; Kuatsjah, E. ; Du, Y. - L. ; Eltis, L. D. ; Ryan, K. S. Snapshots Of The Catalytic Cycle Of An O2, Pyridoxal Phosphate-Dependent Hydroxylase. ACS Chemical Biology 2018, 13, 965-974.
Ryan, K. S. ; Drennan, C. L. Metalloenzymes In Natural Product Biosynthetic Pathways. Natural Product Reports 2018, 35, 612-614.


Du, Y. - L. ; He, H. - Y. ; Higgins, M. A. ; Ryan, K. S. A Heme-Dependent Enzyme Forms The Nitrogen–Nitrogen Bond In Piperazate. Nature Chemical Biology 2017, 13, 836-838.


Du, Y. - L. ; Singh, R. ; Alkhalaf, L. M. ; Kuatsjah, E. ; He, H. - Y. ; Eltis, L. D. ; Ryan, K. S. A Pyridoxal Phosphate–Dependent Enzyme That Oxidizes An Unactivated Carbon-Carbon Bond. Nature Chemical Biology 2016, 12, 194-199.
Du, Y. - L. ; Ryan, K. S. Catalytic Repertoire Of Bacterial Bisindole Formation. Current Opinion in Chemical Biology 2016, 31, 74-81.
Alkhalaf, L. M. ; Du, Y. - L. ; Ryan, K. S. Synthetic Biology Approaches To New Bisindoles. Methods in Enzymology 2016, 4, 682-688.


Du, Y. - L. ; Ryan, K. S. Expansion Of Bisindole Biosynthetic Pathways By Combinatorial Construction. ACS Synthetic Biology 2015, 4, 682-688.
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.
Alkhalaf, L. M. ; Ryan, K. S. Biosynthetic Manipulation Of Tryptophan In Bacteria: Pathways And Mechanisms. Chemistry & Biology 2015, 22, 317-328.
Deng, X. ; Duffy, S. P. ; Myrand-Lapierre, M. E. ; Matthews, K. ; Santoso, A. T. ; Du, Y. - L. ; Ryan, K. S. ; Ma, H. Reduced Deformability Of Parasitized Red Blood Cells As A Biomarker For Anti-Malarial Drug Efficacy. Malaria Journal 2015, 14.


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.
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.


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.
Du, Y. - L. ; Ding, T. ; Patrick, B. O. ; Ryan, K. S. Xenocladoniamide F, Minimal Indolotryptoline From The Cladoniamide Pathway. Tetrahedron Letters 2013.
Du, Y. Ling; Ding, T. ; Ryan, K. S. Biosynthetic O-Methylation Protects Cladoniamides From Self-Destruction. Organic letters 2013, 15, 2538–2541.
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.


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.
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.
Davies, J. ; Ryan, K. S. Introducing The Parvome: Bioactive Compounds In The Microbial World. ACS Chemical Biology 2012, 7, 252 - 259.