Cationic amino acid transporters (CAT) enhance accumulation and susceptibility to the systemic herbicide L-phosphinothricin

Sep 30, 2026

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Cationic amino acid transporters (CAT) are investigated as mediators of the accumulation and susceptibility of the herbicide L-phosphinothricin (PPT). The work links PPT action to irreversible glutamine synthetase (GS) inhibition while comparing Arabidopsis thaliana, Marchantia polymorpha, rice, and Klebsormidium nitens. Resistance in M. polymorpha is explained by deficient PPT uptake, whereas in A. thaliana candidate transporters identified by transcriptomics change PPT accumulation and sensitivity when overexpressed. Key mechanistic residues and helical dynamics in AtCAT5 are analyzed by molecular dynamics, informing herbicide resistance management.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Species-specific susceptibility to PPT

CATs as mediators of PPT accumulation and sensitivity

Article [https://doi.org/10.1038/s41467-025-66840-3](https://doi.org/10.1038/s41467-025-66840-3) Cationic amino acid transporters (CAT) enhance accumulation and susceptibility to the systemic herbicide L-phosphinothricin Received: 26 October 2023 | Accepted: 17 November 2025 | | --- | | | | Check for updates | Grace Zi Hao Tan 1,2, Herrick Yu Kan Koh 1, Zheng Yong Poh1, Yuri Trusov 3, Shalini Krishnamoorthi 1,2, Kasey Goh 1, Célio Cabral Oliveira4, José Ramón Botella 3 & Daisuke Urano 1,2,5 The broad-spectrum herbicide L-phosphinothricin (PPT) irreversibly inhibits glutamine synthetase (GS) activity. Here we present cationic amino acid transporters (CAT) as mediators of PPT accumulation and susceptibility. Comparative analysis of Arabidopsis thaliana, Marchantia polymorpha, rice, and Klebsormidium nitens reveals conserved responses to GS inhibition, with absence of efﬁcient PPT uptake underlying resistance in M. polymorpha. Transcriptomic analysis identiﬁes four candidate transporters in A. thaliana which, when overexpressed in M. polymorpha, confer varying levels of sensitivity corresponding with PPT accumulation. AtCAT1 and AtCAT5 confer the greatest sensitivities and are required for glutamic acid uptake and endogenous nitrogen metabolism inA. thaliana, and PPT susceptibility. Molecular dynamics simulation of AtCAT5 identiﬁes key residues involved in PPT binding, which induce the rotational ﬂexibility of helices H1 and H6 which form an intracellular access tunnel. These ﬁndings highlight the natural diversity underlying PPT accumulation and susceptibility, which can guide herbicide resistance management strategies. Herbicides play a crucial role in modern agriculture, enabling effective weed control and ensuring higher crop yields. Phosphinothricin (PPT), the active compound in herbicides like glufosinate and bialaphos, has become widely utilized due to its broad-spectrum effectiveness, emerging as an alternative to the extensively employed herbicide, glyphosate. With the increasing occurrence of glyphosate resistance, PPT utilization is anticipated to further rise in the coming years, especially with the recent introduction of PPT-resistant crops1. PPT is a glutamate analogue that irreversibly inhibits glutamine synthetase (GS) in plants, disrupting nitrogen metabolism and leading to the accumulation of toxic levels of ammonia and reactive oxygen species2. While enzyme inhibition is the primary mechanism causing cellular damage and plant death, how the herbicide accesses the target enzyme remains unknown. It is generally understood that incidence of herbicide resistant weeds positively correlates with herbicide usage. However, glufosinate remains an anomaly with comparatively few resistant weed populations despite its long history of use2. Such resistant cases were associated with target site mechanisms like altered expression or nonsynonymous mutations in GS3,4. Non-target site resistance mechanisms have yet to be identiﬁed, though reported reductions in PPT uptake and PPT-induced injury by amino acid supplementation have implicated the involvement of amino acid transporters in PPT uptake5,6. For example, PPT uptake in Palmer amaranth was inhibited by glutamine 1Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, Singapore, Singapore. 2Disruptive & Sustainable Technologies for Agricultural Precision (DiSTAP) IRG, Singapore-MIT Alliance of Research and Technology, Singapore, Singapore. 3Plant Genetic Engineering Laboratory, School of Agriculture and Food Sustainability, The University of Queensland, St Lucia, Australia. 4Brazilian Biorenewables National Laboratory(LNBR), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil. 5Department of Biological Sciences, National University of Singapore, 16 Science Drive 4, Singapore, Singapore. e-mail: [daisuke@tll.org.sg](daisuke@tll.org.sg) but not structurally similar amino acids like glutamate, asp

FAQs

What role do cationic amino acid transporters (CAT) play in L-phosphinothricin (PPT) effects?

CATs mediate PPT accumulation and thereby influence herbicide susceptibility. Increased accumulation corresponds to greater sensitivity in the studied systems.

How does PPT resistance differ across the compared plant clades?

The study reports conserved responses to GS inhibition, but resistance in Marchantia polymorpha is linked to the absence of efficient PPT uptake. Other species show sensitivity changes tied to specific transporter activity.

Which findings support the molecular mechanism for PPT binding and uptake?

Molecular dynamics on AtCAT5 identifies key residues involved in PPT binding and shows rotational flexibility of helices that form an intracellular access tunnel, explaining how PPT interacts with the transporter.

Sep 30, 2026

Upload by Ophelia