Cyanogenic glucosides: a lot more than a cyanide bomb!
Birger Lindberg Møller
Plant Biochemistry Laboratory, Department of Plant and Environmental Sciences, University of Copenhagen, Thorvaldsensvej 40, DK-1871 Frederiksberg C, Copenhagen, Denmark
For more than 420 million years, plants, insects and microbes have co-evolved based on a chemical arms race including deployment of refined chemical defense systems by each player. Cyanogenic glucosides (-hydroxynitrile glucosides) are one class of defense compounds produced by numerous plants (e.g. sorghum, barley, wheat, cassava, clover, flax, almonds, eucalypts). Following tissue disruption e.g. caused by a chewing insect, the cyanogenic glucosides are hydrolyzed and release toxic hydrogen cyanide to protect the plant from generalist herbivores. Many fungi are not deterred by hydrogen cyanide which they rapidly convert into carbon dioxide and ammonia.The biosynthetic pathway for cyanogenic glucosides is catalyzed by multifunctional cytochrome P450s (in sorghum: CYP79A1 and CYP71E1) and a UDP-glucosyltransferase (UGT85B1) with E- and Z-oximes as key intermediates. The biosynthetic enzymes are organized within a dynamic enzyme complex (metabolon) enabling efficient channeling of the intermediates to the final product. The metabolon has been isolated from sorghum microsomes. In vitro studies show that CYP71E1 is very sensitive to oxygen. In vivo inactivation of CYP71E1 e.g. by the oxidative burst following a fungal infection would result in accumulation of the E-oxime which is a fungal toxin. In contrast, pathogenic fungi are able to detoxify Z-oximes. The genes encoding the biosynthetic enzymes for cyanogenic glucosides are clustered on the genome. Specialized insects like the Six-spot Burnet moth (Zygaena filipendulae) manage to sequester cyanogenic glucosides from their food plant and to use the plant defence compound in their own defence against predators. The insect de novo synthesizes the cyanogenic glucosides if the amounts obtained by sequestering are low. Sufficient levels are important because cyanogenic glucosides play numerous additional intimate roles in the mating process of the insects e.g. as nuptial gifts. In plants, cyanogenic glucosides serve numerous additional metabolic functions in addition to defense. They may function as storage reservoirs of reduced nitrogen and sugar, as quenchers of reactive oxygen species and as signal molecules. In addition to cyanogenic glucosides, some plants like barley and Lotus japonicus also produce - and -hydroxynitrile glucosides. These do not release toxic hydrogen cyanide upon hydrolysis but give rise to the formation of other defense compounds such as furanones. Forage sorghum contains the cyanogenic glucoside dhurrin and following adverse growth conditions, the amounts of HCN released may be toxic to grazing lifestock. In collaboration with Australian researchers, biochemical screens and TILLING approaches have been used to identify a single amino acid change in the CYP79A1 enzyme that resulted in an inactive enzyme and acyanogenic plants.

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