Passive permeability controls synthesis for the allelochemical sorgeoleone in sorghum root exudate

Competition for soil nutrients and water with other plants foster competition within the biosphere for access to these limited resources. The roots for the common grain sorghum produce exudates that are released into the soil to compete with other plants. Sorgoleone is one such compound, which suppresses weed growth near sorghum by acting as a qunione analog and binding to and inhibiting photosystem II during photosynthesis. Since sorghum also grows photosynthetically, and may be susceptible to sorgoleone action if present in tissues above ground, it is essential for sorgoleone to be excreted efficiently. However, since the P450 enzymes that synthesize sorgoleone are intracellular, the release mechanism for sorgoleone remain unclear. In this study, we conducted an in silico survey for sorgoleone and its precursors to passively permeate biological membranes. To enhance simulation accurate, simulation parameters for sorgoleone and its precursors were optimized using CHARMM methodology. These parameters were used to conduct one microsecond of unbiased molecular dynamics simulations to compare the permeability of sorgoleone with its precursors molecules. We find that interleaflet transfer is maximized for sorgoleone, relative to its precursors. To compute a permeability coefficient using the inhomogeneous solubility diffusion model, we determined the free energy and diffusivity through Replica Exchange Umbrella Sampling simulations. The REUS calculations highlight that sorgleone permeates quickly and may form aggregates in solution that lower the dissolved concentration. This suggests that sorgoleone synthesis occurs within sorghum cells and that sorgoleone is exuded by permeating through the cell membrane without the need for a transport protein.