Tel: +44 (0)1603 450334
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.
Group Members :
Stephanie Brown (PhD Harvard)
Lorenzo Caputi (PhD York)
Fernando Geu-Flores (PhD University of Copenhagen)
Dorota Jakubczyk (PhD Universitat Karlsruhe)
Fionn O'Hara (PhD Cambridge)
Nat Sherden (PhD Caltech)
Evangelos Tatsis (PhD University of Ioannina)
Weslee Glenn (BS Hampton College)
Franziska Kellner (Diploma University of Applied Sciences Dresden)
Richard Payne (Degree Oxford)
Anna Stavrindes (Diploma Montpellier)
• Geu-Flores, F., Sherden, N., Courdavault, V., Burlat, V., Glenn, W. S., Wu, C., Nims, E., Cui, Y. and O’Connor, S. E. (2012) An alternative route to cyclic terpenes by reductive cyclization in iridoid biosynthesis. Nature. 492, 138-142.
• Glenn, W. S., Runguphan, W., O’Connor, S. E. (2012) Redesign of a dioxygenase in morphine biosynthesis. Chem. Biol. 19, 674-678.
• 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. 133, 19346 – 19349.
• 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.
• 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.
DellaPenna D., O'Connor S. E. (2012)
Plant science. Plant gene clusters and opiates.
Science 336 (6089) 1648-9
Geu Flores F., Sherden N. H., Courdavault V., Burlat V., Glenn W. S., Wu C., Nims E., Cui Y., O'Connor S. E. (2012)
An alternative route to cyclic terpenes by reductive cyclization in iridoid biosynthesis.
Nature 492 (7427) 138-42
Glenn W. S., Runguphan W., O'Connor S. E. (2012)
Recent progress in the metabolic engineering of alkaloids in plant systems.
Current Opinion in Biotechnology 24 (2) 354-365
Góngora-Castillo E., Childs K. L., Fedewa G., Hamilton J. P., Liscombe D. K., Magallanes-Lundback M., Mandadi K. K., Nims E., Runguphan W., Vaillancourt B., Varbanova-Herde M., Dellapenna D., McKnight T. D., O'Connor S., Buell C. R. (2012)
Development of transcriptomic resources for interrogating the biosynthesis of monoterpene indole alkaloids in medicinal plant species.
PLoS ONE 7 (12) e52506
O'Connor S. E. (2012)
Strategies for engineering plant natural products: the iridoid-derived monoterpene indole alkaloids of Catharanthus roseus.
meth enzymology 515 189-206
Ruff B. M., Bräse S., O'Connor S. E. (2012)
Biocatalytic production of tetrahydroisoquinolines.
Tetrahedron Letters 53 (9) 1071-1074
Runguphan W., Glenn W. S., O'Connor S. E. (2012)
Redesign of a dioxygenase in morphine biosynthesis.
Chemistry & Biology 19 (6) 674-8
Glenn W. S., Nims E., O'Connor S. E. (2011)
Reengineering a tryptophan halogenase to preferentially chlorinate a direct alkaloid precursor.
Journal of the American Chemical Society 133 (48) 19346-9
Hicks M. A., Barber A. E., Giddings L. A., Caldwell J., O'Connor S. E., Babbitt P. C. (2011)
The evolution of function in strictosidine synthase-like proteins.
Proteins 79 (11) 3082-98
Liscombe D. K., O'Connor S. E. (2011)
A virus-induced gene silencing approach to understanding alkaloid metabolism in Catharanthus roseus.
Phytochemistry 72 (16) 1969-77