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Metabolism of the peptide deformylase inhibitor actinonin in tobacco

Published online by Cambridge University Press:  20 January 2017

Cai-Xia Hou ,
Lynnette M. A. Dirk ,
Jack P. Goodman  and
Mark A. Williams
Cai-Xia Hou
Affiliation:
Department of Horticulture, University of Kentucky, Lexington, KY 40546-0091
Lynnette M. A. Dirk
Affiliation:
Department of Horticulture, University of Kentucky, Lexington, KY 40546-0312
Jack P. Goodman
Affiliation:
University of Kentucky Mass Spectrometry Facility, Lexington, KY, 40506-0286
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Abstract

Actinonin is a naturally occurring hydroxamic acid and a potent inhibitor of the essential cotranslational protein processing enzyme peptide deformylase. Actinonin has both pre- and post-emergence herbicidal activity, but it is rapidly metabolized by plants, thus limiting herbicidal efficacy. Studies designed to elucidate the metabolic fate of actinonin revealed that after absorption actinonin was metabolized by tobacco plants with only about 17% of the parent compound remaining 48 h after application. Subcellular fractionation revealed that a microsomal fraction was capable of metabolizing actinonin in vitro. Two actinonin metabolites were isolated by reverse-phase high-performance liquid chromatography and identified by mass spectrometric analyses. The major metabolite was derived from the hydrolysis of the hydroxamate group to its corresponding acid, and a relatively minor metabolite through reduction of the hydroxamate group to the corresponding amide. Both metabolites were functionally inactive as inhibitors of peptide deformylase. These results provide rationale for the low efficacy of actinonin as a broad-spectrum herbicide, and identify functional groups in actinonin targeted by plants during detoxification. This information may facilitate the design and synthesis of actinonin analogues with increased herbicidal efficacy.

Keywords

actinonintobacco, Nicotiana tabacum L. ‘Samsun NN’Peptide deformylase (DEF)high-performance liquid chromatography (HPLC)electrospray ionization (ESI) mass spectrometrymicrosomes
Type
Physiology, Chemistry, Biochemistry
Information
Weed Science , Volume 54 , Issue 2 , April 2006 , pp. 246 - 254
Copyright
Copyright © Weed Science Society of America 

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References

Literature Cited

Bailey, B. A. and Larson, R. L. 1989. Hydroxamic acid glucosyltransferases from maize seedlings. Plant Physiol 90:1071–1076.Google Scholar
Bailey, B. A. and Larson, R. L. 1991. Maize microsomal benzoxazinone N-monooxygenase. Plant Physiol 95:792–796.Google Scholar
Belford, E. J., Dorfler, U., Stampfl, A., and Schroder, P. 2004. Microsomal detoxification enzymes in yam bean (Pachyrhizus erosus (L.) urban). Z. Naturforsch 59:693–700.CrossRefGoogle ScholarPubMed
Bolwell, G. P., Bozac, K., and Zimmerlin, A. 1994. Plant cytochrome p450. Phytochem 37:1491–1506.Google Scholar
Bracchi-Ricard, V., Nguyen, K. T., Zhou, Y., Rajagopalam, P. T. R., Chakrabarti, D., and Pei, D. 2001. Characterization of a eukaryotic peptide deformylase from Plasmodium falciparum . Arch. Biochem. Biophys 396:162–170.Google Scholar
Bradford, M. M. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem 72:248–254.Google Scholar
Broughton, B. J., Chaplen, P., Freeman, W. A., Warren, P. J., Wooldridge, K. R. H., and Wright, D. E. 1975. Studies concerning the antibiotic actinonin. Part VIII. Structure–activity relationships in the actinonin series. J. Chem. Soc. Perkin Trans 1:857–860.Google Scholar
Buxton, J. W. and Jia, W. 1999. A controlled water table irrigation system for hydroponic lettuce production. Proceedings of the International Symposium on Growing Media and Hydroponics. Acta Hort 481:281–298.Google Scholar
Chen, D. Z., Patel, D. V., Hackbarth, C. J., Wang, W., Dreyer, G., Young, D. C., Margolis, P. S., Wu, C., Ni, Z. J., Trias, J., White, R. J., and Yuan, Z. 2000. Actinonin, a naturally occurring antibacterial agent, is a potent deformylase inhibitor. Biochem 39:1256–1262.Google Scholar
Dirk, L. M. A., Williams, M. A., and Houtz, R. L. 2001. Eukaryotic peptide deformylases. Nuclear-encoded and chloroplast-targeted enzymes in arabidopsis. Plant Physiol 127:97–107.CrossRefGoogle ScholarPubMed
Giglione, C., Pierre, M., and Meinnel, T. 2000. Peptide deformylase as a target for new generation, broad spectrum antimicrobial agents. Mol. Microbiol 36:1197–205.CrossRefGoogle ScholarPubMed
Gordon, J. J., Devlin, J. P., East, A. J., Ollis, W. D., Sutherland, I. O., Wright, D. E., and Ninet, L. 1975. Studies concerning the antibiotic actinonin. Part I. The constitution of actinonin. A natural hydroxamic acid with antibiotic activity. J. Chem. Soc. Perkin Trans 1:819–825.Google Scholar
Gordon, J. J., Kelly, B. K., and Miller, G. A. 1962. Actinonin: an antibiotic substance produced by an actinomycete. Nature 195:701–702.Google Scholar
Hackbarth, C. J., Chen, D. Z., Lewis, J. G., Clark, K., Mangold, J. B., Cramer, J. A., Margolis, P. S., Wang, W., Koehn, J., Wu, C., Lopez, S., Withers, G. III, Gu, H., Dunn, E., Kulathila, R., Pan, S. H., Porter, W. L., Jacobs, J., Trias, J., Patel, D. V., Weidmann, B., White, R. J., and Yuan, Z. 2002. N-alkyl urea hydroxamic acids as a new class of peptide deformylase inhibitors with antibacterial activity. Antimicrob. Agents Chemother 46:2752–2764.Google Scholar
Hou, C. X., Dirk, L. M. A., and Williams, M. A. 2004. Inhibition of peptide deformylase in Nicotiana tabacum leads to decreased D1 protein accumulation, ultimately resulting in a reduction of photosystem II complexes. Am. J. Bot 91:1301–1311.Google Scholar
Leighton, V., Niemeyer, H. M., and Jonsson, L. M. V. 1994. Substrate specificity of a glucosyltransferase and an N-hydroxylase involved in the biosynthesis of cyclic hydroxamic acids in gramineae. Phytochem 36:887–892.Google Scholar
Lelievre, Y., Bouboutou, R., Boiziau, J., and Cartwright, T. 1989. Inhibition of synovial collagenase by actinonin. Study of structure/activity relationship. Pathol. Biol. (Paris) 37:43–46.Google Scholar
Madison, V., Duca, J., Bennett, F., Bohanon, S., Cooper, A., Chu, M., Desai, J., Girijavallabhan, V., Hare, R., Hruza, A., Hendrata, S., Huang, Y., Kravec, C., Malcolm, B., McCormick, J., Miesel, L., Ramanathan, L., Reichert, P., Saksena, A., Wang, J., Weber, P. C., Zhu, H., and Fischmann, T. 2002. Binding affinities and geometries of various metal ligands in peptide deformylase inhibitors. Biophys. Chem 101–102:239–247.Google Scholar
Mazel, D., Coic, E., Blanchard, S., Saurin, W., and Marliere, P. 1997. A survey of polypeptide deformylase function throughout the eubacterial lineage. J. Mol. Biol 266:939–949.Google Scholar
Mazel, D., Pochet, S., and Marliere, P. 1994. Genetic characterization of polypeptide deformylase, a distinctive enzyme of eubacterial translation. EMBO J 13:914–923.CrossRefGoogle ScholarPubMed
Muri, E. M. F., Nieto, M. J., Sindelar, R. D., and Williamson, J. S. 2002. Hydroxamic acids as pharmacological agents. Curr. Med. Chem 9:1631–1653.Google Scholar
Peng, S. X., Strojnowski, M. J., Hu, J. K., Smith, B. J., Eichhold, T. H., Wehmeyer, K. R., Pikul, S., and Almstead, N. G. 1999. Gas chromatographic–mass spectrometric analysis of hydroxylamine for monitoring the metabolic hydrolysis of metalloprotease inhibitors in rat and human liver microsomes. J. Chromatogr. B 724:181–187.Google Scholar
Ross, J., Li, Y., Lim, E. K., and Bowles, D. J. 2001. Higher plant glycosyltransferases. Genome Biol 2:3004.1–3004.6.Google Scholar
Schuler, M. A. 1996. The role of cytochrome P450 monooxygenases in plant–insect interactions. Plant Physiol 112:1411–1419.Google Scholar
Serero, A., Giglione, C., and Meinnel, T. 2001. Distinctive features of the two classes of eukaryotic peptide deformylases. J. Mol. Biol 314:695–708.Google Scholar
Siminszky, B., Corbin, F. T., Ward, E. R., Fleischmann, T. J., and Dewey, R. E. 1999. Expression of a soybean cytochrome P450 monooxygenase cDNA in yeast and tobacco enhances the metabolism of phenylurea herbicides. Proc. Natl. Acad. Sci. USA 96:1750–1755.Google Scholar
Sugihara, K., Kitamura, S., Ohta, S., and Tatsumi, K. 2000. Reduction of hydroxamic acids to the corresponding amides catalyzed by rabbit blood. Xenobiotica 30:457–467.Google Scholar
Sugihara, K., Kitamura, S., and Tatsumi, K. 1983. Evidence for reduction of hydroxamic acids to the corresponding amides by liver aldehyde oxidase. Chem. Pharm. Bull 31:3366–3369.Google Scholar
Summers, J. B., Gunn, B. P., Mazdiyasni, H., Goetze, A. M., Young, P. R., Bouska, J. B., Dyer, R. D., Brooks, D. W., and Carter, G. W. 1987. In vivo characterization of hydroxamic acid inhibitors of 5-lipoxygenase. J. Med. Chem 30:2121–2126.Google Scholar
von Rad, U., Hüttl, R., Lottspeich, F., Gierl, A., and Frey, M. 2001. Two glucosyltransferases are involved in detoxification of benzoxazinoids in maize. Plant J 28:633–642.Google Scholar
Wei, Y. and Pei, D. 1997. Continuous spectrophotometric assay of peptide deformylase. Anal. Biochem 250:29–34.Google Scholar
Williams, M. A., Dirk, L. M. A., and Houtz, R. L. 2000. Characterization of a chloroplast-localized peptide deformylase from Arabidopsis thaliana. Plant Physiol 123:S-131. [Abstract].Google Scholar