Repurposed inhibitor of bacterial dihydrodipicolinate reductase exhibits effective herbicidal activity.

Autor: Mackie ERR; School of Agriculture, Food and Wine, Waite Research Institute, University of Adelaide, Waite Campus, Urrbrae, SA, 5064, Australia.; La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, 3086, Australia., Barrow AS; School of Agriculture, Food and Wine, Waite Research Institute, University of Adelaide, Waite Campus, Urrbrae, SA, 5064, Australia.; La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, 3086, Australia., Giel MC; La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, 3086, Australia., Hulett MD; La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, 3086, Australia., Gendall AR; Australian Research Council Industrial Transformation Research Hub for Medicinal Agriculture, AgriBio, La Trobe University, Bundoora, VIC, 3086, Australia.; Department of Animal, Plant and Soil Sciences, La Trobe University, Bundoora, VIC, 3086, Australia., Panjikar S; Australian Synchrotron, ANSTO, 800 Blackburn Road, Clayton, VIC, 3168, Australia.; Department of Molecular Biology and Biochemistry, Monash University, Melbourne, VIC, 3800, Australia., Soares da Costa TP; School of Agriculture, Food and Wine, Waite Research Institute, University of Adelaide, Waite Campus, Urrbrae, SA, 5064, Australia. tatiana.soaresdacosta@adelaide.edu.au.; La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, 3086, Australia. tatiana.soaresdacosta@adelaide.edu.au.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2023 May 22; Vol. 6 (1), pp. 550. Date of Electronic Publication: 2023 May 22.
DOI: 10.1038/s42003-023-04895-y
Abstrakt: Herbicide resistance represents one of the biggest threats to our natural environment and agricultural sector. Thus, new herbicides are urgently needed to tackle the rise in herbicide-resistant weeds. Here, we employed a novel strategy to repurpose a 'failed' antibiotic into a new and target-specific herbicidal compound. Specifically, we identified an inhibitor of bacterial dihydrodipicolinate reductase (DHDPR), an enzyme involved in lysine biosynthesis in plants and bacteria, that exhibited no antibacterial activity but severely attenuated germination of the plant Arabidopsis thaliana. We confirmed that the inhibitor targets plant DHDPR orthologues in vitro, and exhibits no toxic effects against human cell lines. A series of analogues were then synthesised with improved efficacy in germination assays and against soil-grown A. thaliana. We also showed that our lead compound is the first lysine biosynthesis inhibitor with activity against both monocotyledonous and dicotyledonous weed species, by demonstrating its effectiveness at reducing the germination and growth of Lolium rigidum (rigid ryegrass) and Raphanus raphanistrum (wild radish). These results provide proof-of-concept that DHDPR inhibition may represent a much-needed new herbicide mode of action. Furthermore, this study exemplifies the untapped potential of repurposing 'failed' antibiotic scaffolds to fast-track the development of herbicide candidates targeting the respective plant enzymes.
(© 2023. The Author(s).)
Databáze: MEDLINE
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