Glutathione transferases catalyze recycling of auto-toxic cyanogenic glucosides in sorghum.

Cyanogenic glucosides are nitrogen‐containing specialized metabolites that provide chemical defense against herbivores and pathogens via the release of toxic hydrogen cyanide. It has been suggested that cyanogenic glucosides are also a store of nitrogen that can be remobilized for general metabolism via a previously unknown pathway. Here we reveal a recycling pathway for the cyanogenic glucoside dhurrin in sorghum (Sorghum bicolor) that avoids hydrogen cyanide formation. As demonstrated in vitro, the pathway proceeds via spontaneous formation of a dhurrin‐derived glutathione conjugate, which undergoes reductive cleavage by glutathione transferases of the plant‐specific lambda class (GSTLs) to produce p‐hydroxyphenyl acetonitrile. This is further metabolized to p‐hydroxyphenylacetic acid and free ammonia by nitrilases, and then glucosylated to form p‐glucosyloxyphenylacetic acid. Two of the four GSTLs in sorghum exhibited high stereospecific catalytic activity towards the glutathione conjugate, and form a subclade in a phylogenetic tree of GSTLs in higher plants. The expression of the corresponding two GSTLs co‐localized with expression of the genes encoding the p‐hydroxyphenyl acetonitrile‐metabolizing nitrilases at the cellular level. The elucidation of this pathway places GSTs as key players in a remarkable scheme for metabolic plasticity allowing plants to reverse the resource flow between general and specialized metabolism in actively growing tissue