Genetic approaches to impart HPPD tolerance in crop species: progress and prospects

Herbicides that inhibit 4-hydroxyphenylpyruvate dioxygenase (HPPD) are widely used for broad-spectrum weed control; however, the sensitivity of many crop species limits their application, underscoring the need for the development of HPPD-tolerant crops. Although numerous herbicides are commercially available, HPPD inhibitors are particularly effective for controlling weeds resistant to glyphosate, glufosinate, dicamba, and other herbicides, as instances of evolved resistance to HPPD inhibitors remain low. Major genetic strategies for developing HPPD tolerance include the transgenic introduction of microbial HPPD enzymes with reduced herbicide sensitivity, mutagenesis-based approaches that have yielded novel HPPD alleles, and precise genome modification using CRISPR–Cas9 technology. In addition, protein engineering and directed evolution have been employed to generate HPPD variants with reduced inhibitor sensitivity. Future progress will depend on integrating advanced molecular tools with sustainable weed-management practices to ensure durable trait performance, minimize ecological and regulatory concerns, and reduce gene-flow risks associated with herbicide-tolerant crops.