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Article Abstract
Labor shortages threaten global apple production, thereby encouraging new strategies to improve orchard management. The growth of columnar apples, controlled by the MdDOX-Co gene, enables vertical growth with minimal lateral branching, allowing for high-density planting and easier harvesting. MdDOX-Co encodes 2-oxoglutarate-dependent dioxygenase (2ODD, DOX). This study aimed to identify selective chemical inhibitors of MdDOX-Co. We synthesized the parental C6-based analogs featuring a heterocyclic 1,3,4-oxathiazol-2-one ring and evaluated their inhibitory activity. Compounds retaining the 1,3,4-oxathiazol-2-one core exhibited strong in vitro inhibition and promoted seedling elongation in MdDOX-Co overexpressing Arabidopsis. Structure-activity analysis confirmed that the 1,3,4-oxathiazol-2-one ring was essential, with tolerance for side-chain variations, including bulky groups. Selectivity assays indicated minimal off-target effects on the related 2ODD enzymes. Molecular modeling suggested the compatibility of the lead compounds with the MdDOX-Co active site. These findings encourage us to develop MdDOX-Co-targeted agrochemicals to chemically regulate tree architecture and enhance productivity during apple cultivation.
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