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Herbicide-resistance conferred by expression of a catalytic antibody in Arabidopsis thaliana

Abstract

Engineering herbicide resistance in crops facilitates control of weed species, particularly those that are closely related to the crop, and may be useful in selecting lines that have undergone multiple transformation events. Here we show that herbicide-resistant plants can be engineered by designing an herbicide and expressing a catalytic antibody that destroys the herbicide in planta. First, we developed a carbamate herbicide that can be catalytically destroyed by the aldolase antibody 38C2. This compound has herbicidal activity on all three plant species tested. Second, the light chain and half of the heavy chain (Fab) of the catalytic antibody were targeted to the endoplasmic reticulum in two classes of Arabidopsis thaliana transformants. Third, the two transgenic plants were crossed to produce an herbicide-resistant F1 hybrid. The in vitro catalytic activity of the protein from F1 hybrids corroborates that catalytic antibodies can be constitutively expressed in transgenic plants, and that they can confer a unique trait.

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Figure 1: Herbicidal activity of keto-cartamates.
Figure 2: In vitro retroaldolase activity of 38C2 (Fab) extracted from E. coli.
Figure 3: Influence of herbicide 9 on the rooting and development of seedlings of F1 hybrids and control A. thaliana plants.
Figure 4: Retroaldolase activity 38C2 (Fab) extracted from transgenic plants.

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References

  1. Keinan, E. (ed.) Catalytic Antibodies. (VCH-Wiley, Weinheim, Germany, 2005).

    Google Scholar 

  2. Brik, A. & Keinan, E. Catalytic antibodies in natural products synthesis. in Catalytic Antibodies (ed., Keinan, E.) 132–152 (VCH-Wiley, Weinheim, Germany, 2005).

    Chapter  Google Scholar 

  3. Lindner, A.B., Eshhar, Z. & Tawfik, D.S. Catalytic antibodies as mechanistic and structural models of hydrolytic enzymes. in Catalytic Antibodies (ed., Keinan, E.) 418–453, (VCH-Wiley, Weinheim, Germany, 2005).

    Chapter  Google Scholar 

  4. Yin, J. & Schultz, P.G. Immunological evolution of catalysis. in Catalytic Antibodies (ed., Keinan, E.) 1–29 (VCH-Wiley, Weinheim, Germany, 2005).

    Google Scholar 

  5. Amir, R. & Shabat, D. Medicinal potential of catalytic antibodies. in Catalytic Antibodies (ed., Keinan, E.) 284–303 (VCH-Wiley, Weinheim, Germany, 2005).

    Chapter  Google Scholar 

  6. Sebastian, S.A. & Chaleff, R.S. Soybean mutants with increased tolerance for sulfonylurea herbicides. Crop Sci. 27, 948–952 (1987).

    Article  CAS  Google Scholar 

  7. Eastin, E.F. Movement and fate of metribuzin in Tracy and Tracy M soybeans. Proc. South. Weed Sci. Soc. 34, 263–267 (1981).

    Google Scholar 

  8. Darmency, H.M. & Pernes, J. Use of wild Setaria viride (L) Beauv. to improve triazine resistance in cultivated S. italica (L) by hybridization. Weed Res. 25, 175–179 (1985).

    Article  CAS  Google Scholar 

  9. Chaleff, R.S. & Ray, T.B. Herbicide-resistant mutants from tobacco cell cultures. Science 75, 5104–5107 (1984).

    Google Scholar 

  10. Anderson, P.C. Cell culture selection of herbicide tolerant corn and its ramifications. in Proceedings of the Forty-First Annual Corn and Sorghum Industry Research Conferences, Publication No. 41 (American Seed Trade Association, Washington, DC, 1986).

    Google Scholar 

  11. Gressel, J. Conferring herbicide resistance on susceptible crops. in Herbicides and Plant Metabolism, Society for Experimental Biology Seminar Series 38 (ed. Dodge, A.) 239–242, (Cambridge University Press, Cambridge, UK, 1989).

    Google Scholar 

  12. Windsor, B., Roux, S.J. & Lloyd, A. Multiherbicide tolerance conferred by AtPgp1 and apyrase overexpression in Arabidopsis thaliana. Nat. Biotechnol. 21, 428–433 (2003).

    Article  CAS  Google Scholar 

  13. Wentworth, P. et al. Toward antibody-directed “abzyme” prodrug therapy, ADAPT: carbamate prodrug activation by a catalytic antibody and its in vitro application to human tumor cell killing. Proc. Natl. Acad. Sci. USA 93, 799–803 (1996).

    Article  CAS  Google Scholar 

  14. Ostler, E.L., Resmini, M., Brocklehurst, K. & Gallacher, G. Polyclonal catalytic antibodies. J. Immunol. Methods 269, 111–124 (2002).

    Article  CAS  Google Scholar 

  15. Wang, J., Han, Y. & Wilkinson, M.F. An active immunization approach to generate protective catalytic antibodies. Biochem. J. 360, 151–157 (2001).

    Article  CAS  Google Scholar 

  16. Wang, J., Han, Y., Liang, S. & Wilkinson, M.F. Catalytic antibody therapy against the insecticide carbaryl. Biochem. Biophys. Res. Commun. 291, 605–610 (2002).

    Article  CAS  Google Scholar 

  17. Wagner, J., Lerner, R.A. & Barbas, C.F., III. Efficient aldolase catalytic antibodies that use the enamine mechanism of natural enzymes. Science 270, 1797–1800 (1995).

    Article  CAS  Google Scholar 

  18. Shabat, D., Rader, C., List, B., Lerner, R.A. & Barbas, C.F., III. Multiple event activation of a generic prodrug trigger by antibody catalysis. Proc. Natl. Acad. Sci. USA 96, 6925–6930 (1999).

    Article  CAS  Google Scholar 

  19. Shulman, A. Applications of catalytic antibodies. PhD thesis, submitted to the senate of the Technion – Israel Institute of Technology, Haifa, (2000).

    Google Scholar 

  20. Shulman, A., Sitry, D., Shulman, H. & Keinan, E. Highly efficient antibody-catalyzed deuteration of carbonyl compounds. Chemistry 8, 229–239 (2002).

    Article  CAS  Google Scholar 

  21. Tanaka, F., Fuller, R., Shim, H., Lerner, R.A. & Barbas, C.F., III. Evolution of Aldolase antibodies in vitro: correlation of catalytic activity and reaction–based selection. J. Mol. Biol. 335, 1007–1018 (2004).

    Article  CAS  Google Scholar 

  22. Rader, C. et al. A humanized aldolase antibody for selective chemotherapy and adaptor immunotherapy. J. Mol. Biol. 332, 889–899 (2003).

    Article  CAS  Google Scholar 

  23. Tanaka, F., Lerner, R.A. & Barbas, C.F., III. Reconstructing aldolase antibodies to alter their substrate specificity and turnover. J. Am. Chem. Soc. 122, 4835–4836 (2000).

    Article  CAS  Google Scholar 

  24. List, B., Barbas, C.F., III. & Lerner, R. Aldol sensors for the rapid generation of tunable fluorescence by antibody catalysis. Proc. Natl. Acad. Sci. USA 95, 15351–15355 (1998).

    Article  CAS  Google Scholar 

  25. Jobling, S.A. et al. Immunomodulation of enzyme function in plants by single-domain antibody fragments. Nat. Biotechnol. 21, 77–80 (2002).

    Article  Google Scholar 

  26. Ma, J.K. & Hein, M.B. Immunotherapeutic potential of antibodies produced in plants. Trends Biotechnol. 13, 522–527 (1995).

    Article  CAS  Google Scholar 

  27. Artsaenko, A., Kettik, B., Fieldler, U., Conrad, U. & Düring, K. Potato tubers as a biofactory for recombinant antibodies. Mol. Breed. 4, 313–319 (1998).

    Article  CAS  Google Scholar 

  28. Tavladoraki, P. et al. Transgenic plants expressing a functional single-chain Fv antibody are specifically protected from virus attack. Nature 366, 469–472 (1993).

    Article  CAS  Google Scholar 

  29. Strachan, G., Grant, S.D., Longstaff, M., Porter, A.J. & Harris, W.J. Binding characteristics of anti-atrazine monoclonal antibodies and their fragments synthesized in bacteria and plants. Biosens. Bioelectron. 13, 665–673 (1998).

    Article  CAS  Google Scholar 

  30. Hiatt, A., Cafferkey, R. & Bowdish, K. Production of antibodies in transgenic plants. Nature 342, 76–78 (1989).

    Article  CAS  Google Scholar 

  31. Bowdish, K., Tang, Y., Hicks, J.B. & Hilvert, D. Yeast expression of catalytic antibody with chorismate mutase activity. J. Biol. Chem. 266, 11901–11908 (1991).

    CAS  PubMed  Google Scholar 

  32. Tang, Y., Hicks, J.B. & Hilvert, D. In vivo catalysis of a metabolically essential reaction by an antibody. Proc. Natl. Acad. Sci. USA 88, 8784–8786 (1991).

    Article  CAS  Google Scholar 

  33. Miyashita, M., Suzuki, T., Hoshino, M. & Yoshikoshi, A. The organoselenium-mediated reduction of α,β-epoxy ketones, α,β-epoxy esters, and their congeners to β-hydroxy carbonyl compounds: Novel methodologies for the synthesis of aldols and their analogues. Tetrahedron 53, 12469–12486 (1997).

    Article  CAS  Google Scholar 

  34. Clough, S.J. & Bent, A. Floral dip: a simplified method for Agrobacterium-mediated transformation of Arabidopsis thaliana. Plant J. 16, 735–743 (1998).

    Article  CAS  Google Scholar 

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Acknowledgements

E.K. thanks the Israel-US Binational Science Foundation, the German-Israeli Project Cooperation and the Skaggs Institute for Chemical Biology. Y.W. is a Kinamon Foundation Scholar. A.S. is a Clore Foundation Scholar. We thank Einat Brill Almon for assistance with the herbicidal assays.

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Correspondence to Ehud Keinan.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

A general view of the herbicidal activity of propham (P) and compounds 9, 8, 5, and 6 with respect to germination of Arabidopsis (var. Columbia) seeds. (PDF 3593 kb)

Supplementary Fig. 2

Herbicidal activity of 9 with Desiree potato shoots. (PDF 4975 kb)

Supplementary Fig. 3

Inactivation of herbicide 1 by antibody 38C2 as assayed on Lemna cultures. (PDF 1311 kb)

Supplementary Methods (PDF 160 kb)

Supplementary Note 1 (PDF 133 kb)

Supplementary Note 2 (PDF 81 kb)

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Weiss, Y., Shulman, A., Shir, I. et al. Herbicide-resistance conferred by expression of a catalytic antibody in Arabidopsis thaliana. Nat Biotechnol 24, 713–717 (2006). https://doi.org/10.1038/nbt1213

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