For more than 420 million years, plants, insects and their predators have co-evolved based on a chemical arms race including deployment of refined chemical defense systems by each player. Cyanogenic glucosides are produced by numerous plants (e.g. sorghum, barley, cassava, clover, flax, almonds) and by some specialized insects as part of this arms race. The biosynthetic pathway is catalyzed by multifunctional cytochrome P450s (CYP79 and CYP71E) and a UDP-glucosyltransferase with oximes as a key intermediate. The enzymes are thought to be organized within an enzyme complex (metabolon) to ensure rapid metabolism of the toxic pathway intermediates. The genes encoding the biosynthetic enzymes are clustered on the genome. When attacked by fungi able to rapidly detoxify hydrogen cyanide, the second P450 in the pathway may be inactivated by the associated oxygen burst resulting in production of oximes with anti-fungal activity. Following plant tissue disruption the cyanogenic glucosides are hydrolyzed and release toxic hydrogen cyanide to protect the plant from generalist herbivorous insects. When present in crop or feed plants this may pose a significant problem for human and animal consumption. Forage sorghum contains the cyanogenic glucoside dhurrin and following adverse growth conditions, the amounts of HCN released may be toxic to grazing lifestock. In a collaboration headed by Australian researchers, biochemical screens and TILLING approaches have been used to identify a single amino acid change in the CYP79A1enzyme that resulted in an inactive enzyme and acyanogenic plants. Other mutants have been identified that are cyanogenic as seedlings but where the leaves of the mature plants are acyanogenic, an ideal situation for forage production