Hijacking the auxin highway: Substrate Recognition of Phenoxyacetic Acid Herbicides

Auxins are central for plant growth and development and this has been exploited to design herbicides that hijack the auxin transport machinery and signal transduction pathways. Among these auxin herbicides are phenoxyacetic acid herbicides which have been used for decades. Accumulating structural, biochemical, and physiological evidence converges on a model in which phenoxyacetic acid herbicides exploit the endogenous auxin transport machinery, with both AUXIN-RESISTANT1/LIKE-AUX1 (AUX/LAX) importers and PIN-FORMED (PIN) exporters recognizing and transporting these compounds in a manner closely resembling indole-3-acetic acid. Substrate recognition is governed by conserved interactions with the carboxyl group, while affinity and specificity are modulated by hydrophobic interactions with the aromatic moiety, particularly influenced by halogen substitution. Despite this mechanistic similarity, the comparatively low mobility of phenoxyacetic acid herbicides in planta highlights the importance of additional processes such as intracellular sequestration, metabolic conversion, and conjugation, which limit their systemic distribution. Together with the high conservation of the auxin perception machinery, these findings explain why resistance to synthetic auxins predominantly arises through transport- and metabolism-based mechanisms rather than target-site alterations, and they underscore the central role of auxin transporters as key determinants of herbicide activity and selectivity.