Brief Communication | Published:

Metabolic reprogramming of periwinkle plant culture

Nature Chemical Biology volume 5, pages 151153 (2009) | Download Citation

Subjects

Abstract

We transformed an alkaloid biosynthetic gene with reengineered substrate specificity into Catharanthus roseus. The resulting transgenic plant cell culture produced a variety of unnatural alkaloid compounds when cocultured with simple, achiral, commercially available precursors that the reengineered enzyme was designed to accept. This work demonstrates the power of genetic engineering to retailor the structures of complex alkaloid natural products in plant culture.

  • Compound

    Secologanin

  • Compound

    Tryptamine

  • Compound

    5-Chlorotryptamine

  • Compound

    5-Methyltryptamine

  • Compound

    5-Bromotryptamine

  • Compound

    Strictosidine

  • Compound

    10-Chlorostrictosidine

  • Compound

    10-Methylstrictosidine

  • Compound

    10-Bromostrictosidine

  • Compound

    Ajmalicine

  • Compound

    12-Chloroajmalicine

  • Compound

    12-Methylajmalicine

  • Compound

    Tabersonine

  • Compound

    12-Chlorotabersonine

  • Compound

    12-Methyltabersonine

  • Compound

    Serpentine

  • Compound

    Catharanthine

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Acknowledgements

We gratefully acknowledge J. Shanks and C. Peebles (Iowa State) for detailed advice in the transformation procedure. CAMBIA is acknowledged for providing the pCAMBIA vectors, and N.-H. Chua (Rockefeller) is acknowledged for providing pTA7002. We thank L. Smeester (MIT) for assistance with rt-PCR, J.J. Maresh (MIT) for helpful discussions regarding the Agrobacterium transformation and N. Nims (MIT) for helpful suggestions regarding primer design for rt-PCR experiments. N. Yerkes (MIT) generously provided strictosidine standards. We thank T. Kutchan (Danforth Plant Science Center) for suggesting the pCAMBIA vector system. We gratefully acknowledge J. Simpson's (MIT) assistance in obtaining two-dimensional NMR data. This work was supported by the US National Science Foundation (MCB0719120). We acknowledge the US National Institutes of Health and the American Cancer Society for additional support.

Author information

Affiliations

  1. Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue 18-592, Cambridge, Massachusetts 02139, USA.

    • Weerawat Runguphan
    •  & Sarah E O'Connor

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Contributions

W.R. designed and performed all experiments and contributed to data analysis and manuscript writing. S.E.O. was the principal investigator of the project, contributed to data analysis and manuscript writing and provided funding.

Corresponding author

Correspondence to Sarah E O'Connor.

Supplementary information

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    Supplementary Text and Figures

    Supplementary Figures 1–7, Supplementary Table 1 and Supplementary Methods

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DOI

https://doi.org/10.1038/nchembio.141

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