Biography

Office: Chatt G19 (John Innes Centre)

Sarah O’Connor joined the faculty of UEA in 2011, where she is also a Project Leader at the John Innes Centre. She performed her graduate work at both Caltech and the Massachusetts Institute of Technology, and was an Irving Sigal post-doctoral fellow at Harvard Medical School. After her post-doctoral work, she became assistant and then associate professor of Chemistry at MIT. Her work has been recognized by several awards, including an Alfred P. Sloan research fellowship, the American Chemical Society Pfizer Award and the Royal Society Wolfson Research Merit Award.

Her research focuses understanding how natural product pathways work, with a particular emphasis on plant-derived alkaloids. The organization of natural product pathways in plants pose many exciting research challenges that have only begun to be addressed. Her group has made inroads into the mechanistic study of some of the biochemical transformations observed in plant alkaloid biosynthesis, and, in parallel with these efforts, her group has also engineered the substrate specificity of alkaloid biosynthetic enzymes and implemented these enzymes in metabolic engineering efforts. This has led to the successful use of plant tissue for the production of “new-to-nature” compounds. Finally, her group’s research has also begun to address the challenging problem of elucidating the uncharacterized genes of plant metabolic pathways.

Selected publications

A stereoselective hydroxylation step of alkaloid biosynthesis in Catharanthus roseus.
L. A. Giddings, D. K. Liscombe, J. P. Hamilton, K. L. Childs, D. DellaPenna, C. R. Buell, S. E. O’Connor
J. Biol. Chem., 2011, 286, 16751-16757.

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

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

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

All Publications

<- Page 1 of 2 ->

Patron, N. J., Orzaez, D., Marillonnet, S., Warzecha, H., Matthewman, C., Youles, M., Raitskin, O., Leveau, A., Farré, G., Rogers, C., Smith, A., Hibberd, J., Webb, A. A. R., Locke, J., Schornack, S., Ajioka, J., Baulcombe, D. C., Zipfel, C., Kamoun, S., Jones, J. D. G., Kuhn, H., Robatzek, S., Van Esse, H. P., Sanders, D., Oldroyd, G., Martin, C., Field, R., O'Connor, S., Fox, S., Wulff, B., Miller, B., Breakspear, A., Radhakrishnan, G., Delaux, P., Loqué, D., Granell, A., Tissier, A., Shih, P., Brutnell, T. P., Quick, W. P., Rischer, H., Fraser, P. D., Aharoni, A., Raines, C., South, P. F., Ané, J., Hamberger, B. R., Langdale, J., Stougaard, J., Bouwmeester, H., Udvardi, M., Murray, J. A. H., Ntoukakis, V., Schäfer, P., Denby, K., Edwards, K. J., Osbourn, A., Haseloff, J.

(2015)

Standards for plant synthetic biology: a common syntax for exchange of DNA parts,

in New Phytologist

208

(1)

pp. 13-19

Full Text UEA Repository

(Article)

(Published)


Ruff, B., Bräse, S., O'Connor, S.

(2012)

Biocatalytic production of tetrahydroisoquinolines,

in Tetrahedron Letters

53

(9)

pp. 1071-1074

Full Text UEA Repository

(Article)

(Published)


Hicks, M., Barber, A., Giddings, L., Caldwell, J., O'Connor, S., Babbitt, P.

(2011)

The evolution of function in strictosidine synthase-like proteins,

in Proteins: Structure, Function, and Bioinformatics

79

(11)

pp. 3082-3098

Full Text UEA Repository

(Article)

(Published)


Giddings, L., Liscombe, D., Hamilton, J., Childs, K., DellaPenna, D., Buell, C., O'Connor, S.

(2011)

A Stereoselective Hydroxylation Step of Alkaloid Biosynthesis by a Unique Cytochrome P450 in Catharanthus roseus,

in Journal of Biological Chemistry

286

(19)

pp. 16751-16757

Full Text UEA Repository

(Article)

(Published)


Glenn, W., Nims, E., O'Connor, S.

(2011)

Reengineering a Tryptophan Halogenase To Preferentially Chlorinate a Direct Alkaloid Precursor,

in Journal of the American Chemical Society

133

(48)

pp. 19346-19349

Full Text UEA Repository

(Article)

(Published)


Goetz, K., Coyle, C., Cheng, J., O'Connor, S., Panaccione, D.

(2011)

Ergot cluster-encoded catalase is required for synthesis of chanoclavine-I in Aspergillus fumigatus,

in Current Genetics

57

(3)

pp. 201-211

Full Text UEA Repository

(Article)

(Published)


Liscombe, D., O'Connor, S.

(2011)

A virus-induced gene silencing approach to understanding alkaloid metabolism in Catharanthus roseus,

in Phytochemistry

72

(16)

pp. 1969-1977

Full Text UEA Repository

(Article)

(Published)


Runguphan, W., Qu, X., O'Connor, S.

(2010)

Integrating carbon–halogen bond formation into medicinal plant metabolism,

in Nature

468

(7322)

pp. 461-464

Full Text UEA Repository

(Article)

(Published)


Cheng, J., Coyle, C., Panaccione, D., O'Connor, S.

(2010)

Controlling a Structural Branch Point in Ergot Alkaloid Biosynthesis,

in Journal of the American Chemical Society

132

(37)

pp. 12835-12837

Full Text UEA Repository

(Article)

(Published)


Bernhardt, P., Usera, A., O'Connor, S.

(2010)

Biocatalytic asymmetric formation of tetrahydro-β-carbolines,

in Tetrahedron Letters

51

(33)

pp. 4400-4402

Full Text UEA Repository

(Article)

(Published)


Cheng, J., Coyle, C., Panaccione, D., O'Connor, S.

(2010)

A Role for Old Yellow Enzyme in Ergot Alkaloid Biosynthesis,

in Journal of the American Chemical Society

132

(6)

pp. 1776-1777

Full Text UEA Repository

(Article)

(Published)


Coyle, C., Cheng, J., O'Connor, S., Panaccione, D.

(2010)

An Old Yellow Enzyme Gene Controls the Branch Point between Aspergillus fumigatus and Claviceps purpurea Ergot Alkaloid Pathways,

in Applied and Environmental Microbiology

76

(12)

pp. 3898-3903

Full Text UEA Repository

(Article)

(Published)


Liscombe, D., Usera, A., O'Connor, S.

(2010)

Homolog of tocopherol C methyltransferases catalyzes N methylation in anticancer alkaloid biosynthesis,

in Proceedings of the National Academy of Sciences

107

(44)

pp. 18793-18798

Full Text UEA Repository

(Article)

(Published)


O'Connor, S.

(2010)

Alkaloids,

in Comprehensive Natural Products ll.

Elsevier

pp. 977-1007

UEA Repository

(Chapter)

(Published)


Lee, H., Yerkes, N., O'Connor, S.

(2009)

Aza-Tryptamine Substrates in Monoterpene Indole Alkaloid Biosynthesis,

in Chemistry & Biology

16

(12)

pp. 1225-1229

Full Text UEA Repository

(Article)

(Published)


Bernhardt, P., O'Connor, S.

(2009)

Synthesis and biochemical evaluation of des-vinyl secologanin aglycones with alternate stereochemistry,

in Tetrahedron Letters

50

(51)

pp. 7118-7120

Full Text UEA Repository

(Article)

(Published)


Bernhardt, P., O'Connor, S.

(2009)

Opportunities for enzyme engineering in natural product biosynthesis,

in Current Opinion in Chemical Biology

13

(1)

pp. 35-42

Full Text UEA Repository

(Article)

(Published)


Bernhardt, P., Yerkes, N., O'Connor, S.

(2009)

Chemo-enzymatic synthesis of heteroyohimbine alkaloid stereoisomers,

in Organic & Biomolecular Chemistry

7

pp. 4166-4168

Full Text UEA Repository

(Article)

(Published)


Friedrich, A., Bräse, S., O'Connor, S.

(2009)

Synthesis of 4-, 5-, 6-, and 7-azidotryptamines,

in Tetrahedron Letters

50

(1)

pp. 75-76

Full Text UEA Repository

(Article)

(Published)


Leonard, E., Runguphan, W., O'Connor, S., Prather, K.

(2009)

Opportunities in metabolic engineering to facilitate scalable alkaloid production,

in Nature Chemical Biology

5

(5)

pp. 292-300

Full Text UEA Repository

(Article)

(Published)


<- Page 1 of 2 ->

Key Research Interests

Plants and microbes produce an enormous number of complex molecules called secondary (specialized) metabolites or natural products. These compounds play varied and rich roles to enhance the fitness of the producing organism. Moreover, many of these products that nature has provided have life-saving properties and are used extensively in both traditional and modern medicine. Examples of natural products that are used clinically include vinblastine (a chemotherapy agent), morphine (an analgesic), Taxol (a chemotherapy agent) and artemisinin (an anti-malarial). Despite the importance of natural products for a wide variety of industrial applications, many natural product pathways remain poorly understood. We are developing approaches to elucidate and manipulate specialized plant metabolism to 1) understand the fundamental biochemical processes that underlie their biosynthesis and 2) to enable development of platforms that will allow of fast and inexpensive production of these compounds. We also, in collaboration with other groups, investigate the biochemistry of certain natural product biosynthetic pathways from filamentous fungi that act as plant pathogens.

For more information about our research into:

  • Metabolic Pathway Elucidation in Medicinal Plants
  • Synthetic Biology with Metabolic Pathways
  • Enzyme Biochemistry, Mechanism and Evolution


Please see our group webpage at http://www.jic.ac.uk/staff/sarah-oconnor.

Current Support

BB/J009091/1
04/12 – 04/15
BBSRC (funded- awaiting confirmation of final amount of award)
Towards Plant Synthetic Biology: Elucidating the Novel Enzymology of Iridoid Biosynthesis
This project describes uncovering the enzymology of terpene biosynthesis.

RO1-GM074820-04 (O’Connor, PI)
04/01/07 – 02/29/12
NIH $1,466,142
Early Steps in Alkaloid Biosynthesis
This project describes the use of biosynthetic pathways to make new natural products by precursor directed biosynthesis.

1RC2GM092521 (Chappell, U. KY, Program Director; Della Penna, MSU; O’Connor, MIT co-Program Directors)
09/30/09 – 09/29/12
NIH $595,681
Advancing Drug Development in Medicinal Plants Using Transcriptomics and Metabolomics
This multi-investigator proposal describes the transcriptional and metabolic profiling of medicinal plant species.

Past Support

RO1-GM074820-03S1 (O’Connor, PI)
07/15/09 – 06/30/10
NIH $106,458
Early Steps in Alkaloid Biosynthesis
This award was an Administrative Supplement.

RSG-07-025-01 (O’Connor, PI)
01/01/07-12/31/10
American Cancer Society $720,000
Production of Vinblastine Analogues in Madagascar Periwinkle
This project described the chemoenzymatic synthesis and biological assay of anhydrovinblastine and vinblastine analogues.

MCB-0719120 (O’Connor, PI)
10/01/07-09/30/10
NSF $445,856
Combinatorial Biosynthesis of New Alkaloids in Periwinkle
This project described transformation of new enzymes into periwinkle to generate genetically engineered plant cell cultures that make new natural products.

Sloan Fellowship (O’Connor, PI)
09/16/07-09/15/09
Alfred P. Sloan Foundation $22,500
Research Fellowship
This award was unrestricted.

(O’Connor, PI)
05/01/07-04/30/08
David Koch Research Fund $100,000
Harnessing the Production of Anti-Cancer Agents from Plants
This project described synthesis of new alkaloid biosynthesis starting materials.

(O’Connor PI)
07/01/06 – 06/30/08
J. J. and E.V. Wade Fund $25,000
Directed Biosynthesis of Terpene Indole Alkaloids
This project described the directed biosynthesis of terpene indole alkaloids in C. roseus

(O’Connor PI)
09/01/06 – 08/31/08
Paul Cook Innovation Fund $15,000
This project described redesign of a central enzyme in alkaloid biosynthesis: implication for plant metabolic engineering.

(O’Connor, PI)
09/15/05-09/14/08
Beckman Foundation $88,000
Natural Product Diversity
This project outlined the development of new methods to stimulate natural product production in microbes.

(O’Connor, award)
Latham Family Career Development
07/01/04-06/30/07
Latham Family Endowment $60,000
This award was unrestricted.

(O’Connor, PI)
07/01/04-08/31/06
Petroleum Research Fund $35,000
Characterization of Strictosidine Synthase, A Key Enzyme in Alkaloid Biosynthesis
This grant described the initial characterization of strictosidine synthase.

(O’Connor, PI)
12/01/03-11/30/05
Smith Family Foundation $200,000
Human Biosynthesis of Alkaloids
This proposal described elucidating the function of human homologues to plant biosynthetic enzymes.

(O’Connor, PI)
07/01/04
3M Innovation Fund $50,000
Early Steps of Terpene Indole Alkaloid Biosynthesis
This proposal described mechanistic studies of the second enzyme of the terpene indole alkaloid pathway, strictosidine glucosidase.

(O’Connor, PI)
07/01/04
Ferry Fund $50,000
Alkaloid Biosynthesis
This grant supported research on mechanistic studies of strictosidine synthase.

(O’Connor, award)
Amgen New Faculty Award (09/30/03) - $10,000: Amgen’s Chemistry Research and Discovery Department
This award was unrestricted.

Research Group Membership

Members of the O’Connor Group

Sarah E. O’Connor
Project Leader
Email: Sarah.O’Connor@bbsrc.ac.uk
Tel: +44 (0)1603 450334
Sarah O’Connor’s CV (pdf)

John Cheng
Post-doc
Email: jzc@mit.edu

Fernando Geu-Flores
Post-doc
Email: Fernando.Geu-Flores@bbsrc.ac.uk

Weslee Glenn
PhD student
Email: Weslee.Glenn@bbsrc.ac.uk

Nat Sherden
Post-doc
Email: Nat.Sherden@bbsrc.ac.uk

O’Connor Group Alumni

PhD students
2003-2008 Elizabeth McCoy (BA Hamline College) - currently a postdoc at Dartmouth University
2005-2010 Peter Bernhardt (MS University of Minnesota) - currently a postdoc at Scripps Oceanography
2005-2011 Lesley Ann Giddings (BS Smith College) - currently a postdoc at NIH
2005-2010 Nancy Yerkes (BS Columbia University) - currently a medical student at Stanford
2006-2011 Weerawat Ricky Runguphan (BS Harvard University) - currently a postdoc at Stanford University
2007-2011 Johnathan Cheng (BS University of Hawaii) - currently a postdoc at JIC

Post-Doctorals
2005-2006 Carman Galan (PhD University of Georgia) - currently on the faculty at Bristol University, UK
2005-2007 Shi Chen (PhD Shanghai Jiaotong University) - currently on the faculty at Wuhan University, China
2004-2008 Justin Maresh (PhD University of Chicago) - currently on the faculty at DePaul University, USA
2007-2008 Xudong Qu (PhD Shanghai Institute of Organic Chemistry) - currently on the faculty at Shanghai Institute of Organic Chemistry, China
2007-2011 Aimee Usera (PhD Johns Hopkins University) - currently a project leader at Norvartis, Cambridge, USA
2008-2011 Hyang Yeol Lee (PhD University of Michigan) - currently on the faculty at Chungju National University, Korea
2008- 2011 Nathan Nims (PhD UMass Amherst) - currently a project leader at Ra Biotech, Cambridge, USA
2009- 2011 David Liscombe (PhD University of Calgary) - currently a postdoc at Salk Institute, USA

Visiting Students
2008-2009 Anne Friedrich (PhD student Universitat Karlsruhe)
2010-2011 Bettina Ruff (PhD student Universitat Karlsruhe)

External Activities and Indicators of Esteem

  • Invited Lectures:
  • enGENEious Conference, University of Oxford, Oxford, UK, 6/12
  • 47th Bürgenstock Conference, Brunnen, Switzerland, 04/12
  • Systems Biology Workshop, Hong Kong, 12/11
  • University of Ghent, Ghent, Belgium, 12/11
  • Smart Cell Symposium 12/11
  • Oxford Botanical Gardens, Oxford, UK, 10/11
  • Dorothy Crowfoot-Hodgkin (DCH) symposium, Zurich, Switzerland, 10/11
  • University of Missouri, Department of Plant Biology, Columbus, MO 9/11
  • American Chemical Society, Pfizer Award Lecture, Denver, CO 8/11
  • American Society of Pharmacognosy, Plenary Speaker, San Diego, CA 08/11
  • University of Kentucky, Department of Plant and Soil Science, Lexington, KY, 01/11
  • Biotrends Symposium, Keynote Speaker, Dortmund, Germany, 12/10
  • New Horizons in Natural Product Chemistry, Nottingham, UK 11/10
  • Synthetic Biology International Workshop, Plenary Speaker, Copenhagen, Denmark, 8/10
  • 2010 Gordon Research Conference on Stereochemistry, Newport, RI, 8/10
  • 2010 Trends in Enzymology, Plenary Speaker, Ascona, Switzerland, 6/10
  • Washington State, Institute of Biological Chemistry, Pullman, WA, 5/10
  • Advances in Chemical Sciences Symposium, Plenary Speaker, Boston, MA, 4/10
  • University of Illinois, Chemistry Department, 3/10
  • University of Colorado, Chemistry Department, Boulder, CO, 3/10
  • Colorado State University, Chemistry Department, Fort Collins, CO, 3/10
  • University of Kansas, Newmark Lecture in Biochemistry, 2/10
  • UCLA, Chemistry Department, 2/10
  • UC Berkeley, Chemistry Department, Abbott Laboratories Lecture, Berkeley, CA, 1/10
  • 2009 International Plant Biology Congress, St Louis, MO, 10/09
  • Stanford University, Chemistry Department, Palo Alto, CA, 10/09
  • 2009 Nature Chemical Biology Symposium, Chemical Biology in Drug Discovery, Cambridge, MA, 9/09
  • Canadian Plant Genomics Workshop, Plenary Speaker, Saskatchewan, Canada, 8/09
  • American Chemical Society, for “Natural Products”, Division of Biological Chemistry, Salt Lake City, UT, 8/09
  • American Chemical Society, for “Natural Products”, Division of Biological Chemistry, Salt Lake City, UT, 8/09
  • 2009 Gordon Research Conference on Plant Metabolic Engineering, 7/09
  • 2009 Gordon Research Conference on Heterocycles, 6/09
  • Caltech, Chemistry Department, Pasadena, CA, 6/09
  • Boston University, Chemistry Department, Boston, MA, 3/09
  • Indiana University, Chemistry Department, Bloomington, IN, 3/09
  • Schering Plough Medicinal Chemistry Division, Cambridge, MA, 02/09
  • University of Minnesota, Biotechnology Institute Seminar, Minneapolis, MN, 02/09
  • Brandeis University Chemistry Department, Boston, MA, 2/09
  • Philadelphia Organic Chemists Club Seminar Series, Philadelphia, PA, 1/09
  • Case Western Reserve, Chemistry Department, Cleveland, OH, 12/08
  • Eli Lilly, Indianapolis, IN, 8/08
  • Scripps Research Institute, La Jolla, CA, 8/08
  • 2008 Transatlantic Frontiers of Chemistry Conference, 8/08
  • 2008 Gordon Research Conference on Enzymes, Coenzymes and Metabolic Pathways, 7/08
  • 2008 Northeast Regional Meeting of the American Chemical Society, Burlington, VT, 7/08
  • 2008 Gordon Research Conference on Natural Products Chemistry, 7/08
  • Engineering Foundation Conference, Whistler, BC, 6/08
  • 2008 Gordon Research Conference on Bioorganic Chemistry, 6/08
  • Harvard Medical School, BCMP Department, Boston, MA, 6/08
  • University of Pittsburgh Paul Dowd Lecturer, Chemistry Department, Pittsburgh, PA, 5/08
  • Johns Hopkins University School of Medicine, Department of Pharmacology, Baltimore, MD, 5/08
  • 91st Canadian Chemistry Conference, Edmonton, CA, 5/08
  • Cornell University, Chemistry Department, Ithaca, NY, 4/08
  • University of Massachusetts Amherst, Molecular Cell Biology Program, Amherst, MA, 4/08
  • American Chemical Society, for “Optimizing Nature's Privileged Structures: Biosynthesis and Semisynthetic Advances”, Division of Medicinal Chemistry, New Orleans, LA, 4/08
  • Vanderbilt University, Chemistry Department, Nashville, TN, 3/08
  • University of Wisconsin, Chemical Biology Program, Madison, WI, 2/08
  • Harry and Elsa Jiler American Cancer Society Meeting (invited poster), Naples, FL, 11/07
  • University of Rochester, Chemistry Department, Rochester, NY, 11/07
  • Brown University, Chemistry Department, 10/07
  • 2007 Phytochemical Society of North America, St. Louis, MO, 7/07
  • NSF Workshop on Organic Synthesis, Estes Park, CO, 6/07
  • US-China Early Career Workshop on Chemical Biology, Shanghai, China, 5/07
  • Washington University, Chemistry Department, St. Louis, MO, 1/07
  • Danforth Plant Science Center, St. Louis, MO, 1/07
  • University of California, Department of Pharmaceutical Chemistry, San Francisco, CA, 11/06
  • University of Mainz, Department of Pharmacy, Mainz, Germany, 10/06
  • Society for Industrial Microbiology, Annual Meeting, Baltimore, MD, 8/06
  • European Symposium on Bio-Organic Chemistry, Gregynogg, Wales, 5/06
  • 2005 Phytochemical Society of North America, La Jolla, CA, 7/05
  • Invited Reviews:
  • O’Connor, S. E. “Alkaloids” in Comprehensive Natural Products II L. Mander, H.-W. Lui, Eds. Elsevier: Oxford, 2010; Vol. 1, pp. 977-1007.
  • 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.
  • O’Connor, S. E. (2008) Alkaloid Biosynthesis. in: Encyclopedia of Chemical Biology. WileyBlackwell, T. Begley Ed.
  • McCoy, E., O’Connor, S. E. (2008) Natural products from plant cell culture. Prog Drug Res. 65, 331 - 70.
  • O'Connor, S. E., Maresh, J. M. (2006) Chemistry and biology of terpene indole alkaloid biosynthesis. Nat. Prod. Rep. 23, 532 - 547.

Professional Activities

  • Editorial Board Member Natural Products Reports (2011 - present)
  • Editorial Board Member Frontiers in Plant Science (2010 - present)
  • Member of the Scientific Advisory Board of Alkion (2011 - present)
  • Vice chair (2013) and chair (2015) of the Plant Metabolic Gordon Research Conference
  • Organizing Committee for Banff (2012)
  • Organizing Committee for European Conference on Natural Products (2013)