• Sarah O'Connor's Research

Related links

• AT JIC:
• Biological Chemistry
• ON THE WEB:
• Medicinal Plant Genomics Resource
• Plant Engine COST Action

Curriculum Vitae

• 1995 BS University of Chicago, USA
• 2001 PhD Massachusetts Institute of Technology, USA
• 2001 Irving Sigal Postdoctoral Fellow, Harvard Medical School, USA
• 2003 - 2007 Assistant Professor of Chemistry, Massachusetts Institute of Technology, USA
• 2007 - 2011 Associate Professor of Chemistry, Massachusetts Institute of Technology, USA
• 2011 - present Project Leader, John Innes Centre, UK
• 2011 - present Synergy Lecturer in Chemistry, University of East Anglia, UK

Sarah O'Connor

Project Leader

Biological Chemistry

Contact details

Tel: +44 (0)1603 450334
Sarah.O'Connor@jic.ac.uk

Research interests

Plants produce hundreds of thousands of complex metabolites– "natural products"– that are used in a wide variety of industrial applications. Natural products are, for example, a rich source of pharmaceuticals. Anti-cancer agents such as vinblastine and taxol, the analgesic morphine, and the anti-malarials artemisinin and quinine are each natural products that are produced by a plant.

Despite the importance of these compounds, it remains unclear how many of these complicated molecules are made by the plant. The major focus in our group is to elucidate, understand, and engineer the metabolic pathways that construct these compounds from simple building blocks. An understanding of these pathways will allow us to fully harness the wealth of compounds and biocatalysts that plants have provided. Moreover, we can also begin to speculate how and why plants evolved to produce some of these molecules. We take a multi-disciplinary approach to answering research questions, using plant molecular biology, enzymology and chemical strategies in our group.

For example, we create transgenic plants and plant tissue capable of producing “new-to-nature products”, focusing on the medicinal plant Catharanthus roseus, or Madagascar periwinkle. We also explore the mechanism and engineer the substrate specificity of plant biosynthetic enzymes to use in these metabolic engineering efforts. Additionally, we are working to rapidly elucidate key steps in plant metabolic pathways using state-of-the-art sequencing and bioinformatics approaches. A large scale project to obtain the transcriptomes of 14 medicinal plants is allowing us to elucidate the genes involved in C. roseus pathways, and metabolite profiling data of these plant tissues is allowing us to build correlations between gene expression and metabolite production. For more information, see http://medicinalplantgenomics.msu.edu.

Understanding the pathways, genes and enzymes that catalyze biosynthetic processes is now enabling us to use synthetic biology approaches to overproduce these valuable plant-derived compounds in more tractable plant (e.g. Nicotiana benthamiana) or microbial (e.g. yeast) host organisms, and may also facilitate reprogramming of biosynthetic pathways to produce "unnatural" natural products with improved bioactivities.

We also study alkaloid biosynthesis in filamentous fungi that act as plant pathogens, in collaboration with the Panaccione group at West Virginia. The ergot alkaloids are tryptophan-derived compounds that have powerful biological activities- LSD is perhaps the most famous of the ergot alkaloids! With our coworkers, we have elucidated the mechanisms of some of the enzymes involved in forming these compounds.

Selected Publications:

Ruff, B. M. Brase, S., O’Connor, S. E.^‡ (2012) Biocatalytic production of tetrahydroisoquinolines. Tetrahedron Lett. in press

Glenn, W., Nims, N. E., O'Connor, S. E.^‡ (2011) Reengineering a tryptophan halogenase to preferentially chlorinate a direct alkaloid precursor. J. Am. Chem. Soc. in press.

Hicks, M. A., Barber II, A. E., Giddings, L. A., O’Connor, S. E., Babbitt P. C.^‡ (2011) The evolution of function in strictosidine synthase-like proteins. Proteins. 79, 3082 – 3098.

Liscombe, D. K., O’Connor, S. E.^‡ (2011) A virus-induced gene silencing approach to understanding alkaloid metabolism in Catharanthus roseus. Phytochemistry, 72, 1969 – 1977.

Goetz, K. A., Coyle, C. M., Cheng, J. Z., O’Connor, S. E., Panaccione, D. M.^‡ (2011) Ergot cluster-encoded catalase is required for synthesis of chanoclavine-I in Aspergillus fumigatus. Curr. Gen. 57, 201 – 211.

Giddings, L. A., Liscombe, D. K., Hamilton, J. P., Childs, K. L., DellaPenna, D., Buell, C. R., O’Connor, S. E.^‡ (2010) A stereoselective hydroxylation step of alkaloid biosynthesis in Catharanthus roseus. J. Biol. Chem. 286, 16751 – 16757.

Runguphan, W., Xudong, Q., O’Connor, S. E.^‡ (2010) Integrating carbon – halogen bond formation into medicinal plant metabolism. Nature 468, 461 – 464.

Liscombe, D. K. Usera, A. R., O’Connor, S. E.^‡ (2010) A homolog of tocopherol C-methyltransferases catalyzes N-methylation in anticancer alkaloid biosynthesis. Proc. Natl. Acad. Sci. USA 107, 18793 – 18798.

Cheng, J. Z., Coyle, C. M., Panaccione, D. M., O’Connor, S. E.^‡ (2010) Controlling a structural branch point in ergot alkaloid biosynthesis. J. Am. Chem. Soc. 132, 12835 – 12837.

Bernhardt, P., Usera, A. R., O’Connor, S. E^.‡ (2010) Biocatalytic asymmetric formation of tetrahydro-beta-carbolines. Tetrahedron Lett. 51, 4400 – 4402.

Coyle, C. M., Cheng, J. Z., O’Connor, S. E., Panaccione, D. M.^‡ (2010) An old yellow enzyme required for ergot alkaloid biosynthesis in Aspergillus fumigatus and its role at the branch point between A. fumigatus and Claviceps purpurea ergot alkaloid pathways. App. Environ. Microbiol. 76, 3898 – 3903.

Cheng, J. Z., Coyle, C. M., Panaccione, D. M.^‡, O’Connor, S. E.^‡ (2010) A role for old yellow enzyme in ergot alkaloid biosynthesis. J. Am. Chem. Soc. 132, 1776 – 1777.

O’Connor, S. E.^‡ “Alkaloids” in Comprehensive Natural Products II L. Mander, H.-W. Lui, Eds. Elsevier: Oxford, 2010; Vol. 1, pp. 977–1007.

Bernhardt, P., O'Connor, S. E.‡ (2009) Synthesis and biochemical evaluation of des-vinyl secologanin aglycones with alternate stereochemistry. Tetrahedron Lett. 50, 7118 – 7120.

Lee, H.-Y., Yerkes, N., O’Connor, S. E.^‡ (2009) Aza-tryptamine substrates in monoterpene indole alkaloid biosynthesis. Chem. Biol. 16, 1225 – 1229.

Runguphan, W., Maresh, J. J., O’Connor, S. E.^‡ (2009) Silencing of tryptamine biosynthesis for production of unnatural alkaloids in plant culture. Proc. Natl. Acad. Sci. USA 106, 13673 – 13678.

Bernhardt, P., Yerkes, N., O’Connor, S. E.^‡ (2009) Bypassing stereoselectivity in the early steps of alkaloid biosynthesis. Org. Biomol. Chem. 7, 4166 – 4168.

Usera, A. R., O'Connor, S. E. ^‡ (2009) Mechanistic advances in plant natural product enzymes. Curr. Opin. Chem. Biol. 13, 485 – 491. 

Leonard, E., Runguphan, W., O’Connor, S., Prather, K. J.^‡ (2009) Opportunities in metabolic engineering to enable scalable alkaloid production. Nat. Chem. Biol. 5, 292 – 300.

Bernhardt, P., O’Connor, S. E.^‡ (2009) Opportunities for enzyme engineering in natural product biosynthesis. Curr. Opin. Chem. Biol. 13, 35 – 42.

Runguphan, W., O’Connor, S. E. ^‡ (2009) Metabolic reprogramming of periwinkle plant culture. Nat. Chem. Biol. 5, 151 – 153.

Friedrich, A., Brase, S., O’Connor, S. E. ^‡ (2009) Synthesis of 4-, 5-, 6- and 7-azido tryptamines, Tetrahedron Lett. 50, 75 – 76.

O’Connor, S. E. ^‡ (2009) peer reviewed chapter “Elucidation of Natural Product Pathways in Plants" for "Plant-derived natural products; Synthesis, function and application" Springer, A. E. Osbourn, V. Lanzotti, Ed.