Cardenolide biosynthesis in foxglove

Abstract

The article reviews the state of knowledge on the biosynthesis of cardenolides in the genus Digitalis. It summarizes studies with labelled and unlabelled precursors leading to the formulation of the putative cardenolide pathway. Alternative pathways of cardenolide biosynthesis are discussed as well. Special emphasis is laid on enzymes involved in either pregnane metabolism or the modification of cardenolides. About 20 enzymes which are probably involved in cardenolide formation have been described 'downstream' of cholesterol, including various reductases, oxido-reductases, glycosyl transferases and glycosidases as well as acyl transferases, acyl esterases and P450 enzymes. Evidence is accumulating that cardenolides are not assembled on one straight conveyor belt but instead are formed via a complex multidimensional metabolic grid. For example 'fucose-type' cardenolides and 'digitoxosetype; cardenolides seem to form via different biosynthetic branches and the 'norcholanic acid pathway' identified recently seems to be operative only in the formation of fucose-type cardenolides.