Exploring the Molecular Basis of Multiple Herbicide Resistance in Black Grass (Alopecurus myosuroides)

Modern agriculture couples the management of invasive weed species with enhancing crop yields through the intensive use of herbicides. As a result of herbicides being the primary method of weed control in agronomic crops, herbicide resistance has evolved and there has been a vast increase in the occurrence and distribution of herbicide resistant weeds. Many of the most problematic weeds have now evolved multiple herbicide resistance (MHR), which is associated with an enhanced ability to detoxify xenobiotics, enabling the weed to survive herbicide application irrespective of the mode of action. As herbicide resistance is a major limiting factor to food security in global agriculture, effective methods for weed management are sought. This work focuses on MHR in black grass (Alopecurus myosuroides), one of the most damaging weeds of winter cereals. Previous work by Edwards et al. described that black grass populations showing MHR, exhibit an upregulation in the expression of a specific phi-class glutathione transferase (AmGSTF1), which is thought to have a direct regulatory control on metabolism. The importance of AmGSTF1 in MHR has been confirmed both genetically by transgene experiments and chemically through inhibition experiments. This offers the opportunity to develop potential herbicide synergists, which are active towards AmGSTF1 and restore herbicide control in multiple herbicide resistant black grass. Considering the rapid spread of MHR in grass weeds and the limited development of new herbicides, synergists offer an important alternative strategy in counteracting resistance in the field. Recently a new class of AmGSTF1 inhibitors, derived from flavonoids, could be identified. Initial efforts focused on the synthesis of a series of flavone analogues, mainly with structural changes of the C-ring and different substituents in the 5-position. A particular emphasis was put on increasing the aqueous solubility and other physicochemical properties of the compounds, in order to increase the bioavailability in the plant. Although the potency of the initial lead molecule could not be increased in vitro, 5,7-dimethoxy-2-(1’,3’-thiazol-2’-yl)-4H-chromen-4-one, with a significantly increased aqueous solubility, showed good results in in vivo studies in black grass and acted as a synergist to the herbicide pinoxaden. The black grass plants died, when pinoxaden (10μl of a 15 μM solution) was applied to plants, which were pre-treated with the thiazole (10 μl of a 2 mM solution), but survived the herbicide treatment, if no synergist was applied prior