Pathway Mining Reveals Novel Insights into Iron and Zinc Accumulation in Sorghum

Sorghum, resilient and vital in tropics, suits biofortification against hidden hunger. This paper advances beyond a review of current strategies, offering a genomic approach to identify iron and zinc bioaccumulation genes. Utilizing ‘chromosome strolling’ and ‘pathway mining’ (a manual, databasedriven analyses within SorghumCyc, a PathoLogicgenerated resource), we systematically screened chromosomes and metabolic pathways. This methodology facilitates the discovery of previously uncharacterized genes, pathways, and proteins potentially involved in the iron and zinc accumulation, thereby expanding the genetic toolkit for sorghum biofortification. Pathway mining revealed a putative link between the terminal steps of the porphyrin biosynthesis pathway, specifically ferroptosis and the Fenton reaction, and iron accumulation. Ferroptosis releases ferrous iron (Fe²), while the Fenton reaction generates ferric iron (Fe³). While these free iron ions induce programmed cell death in animals, we hypothesize that in plants, they are chelated and sequestered within grains. This study presents the first report implicating ferroptosis and the Fenton reaction in plant iron accumulation. Furthermore, we propose novel pathways, including ascorbate ferrireductase activity, heme oxygenase-mediated decyclization, and phytochromobilin biosynthesis, along with specific genes (Sobic.006G093100, Sobic.006G218050, Sobic.010G184600, Sobic.001G347800, Sobic.010G184800, Sobic.001G527600 for iron; Sobic.003G210000 and Sobic.007G028600 for zinc), as potential contributors to iron and zinc accumulation. By elucidating the genetic mechanisms governing nutrient biosynthesis and employing comparative genomics to identify and integrate orthologous genes from model organisms, we aim to accelerate the development of nutritionally enhanced sorghum varieties through targeted biofortification.