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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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