PRAVASTATIN - A TOOL FOR INVESTIGATING THE AVAILABILITY OF MEVALONATEMETABOLITES FOR PRIMARY AND SECONDARY METABOLISM IN CATHARANTHUS-ROSEUS CELL-SUSPENSIONS

In the C20 strain of Catharanthus roseus, 2,4-dichlorophenoxyacetic ac id (2,4-D) reduces alkaloid accumulation by inhibiting the synthesis o f precursors of alkaloid terpenoids. However, the presence of this gro wth regulator is necessary to promote growth, as measured in terms of dry weight and sterol content. The terpenoid metabolism implicated in the accumulation of alkaloids would therefore be the target of 2,4-D i nhibition and not the metabolism leading to sterol biosynthesis. The s pecific inhibition by pravastatin of 3-hydroxy-3-methylglutaryl CoA re ductase (EC 1.1.1.34), the enzyme that catalyses mevalonate synthesis, enables the limitation of mevalonate on sterol content and on alkaloi d accumulation to be studied. In presence of pravastatin cells are sup plied with labelled mevalonate. Under these conditions the mevalonate is incorporated into sterols but not into alkaloids accumulated in the absence of 2,4-D. The inhibition of sterol biosynthesis induced by pr avastatin is not overcome by zeatin or a cytokinin-like compound, wher eas the inhibition of alkaloid accumulation can be partially overcome. The use of pravastatin shows that the availability of mevalonate for primary and secondary metabolism is differently regulated in Catharant hus roseus cells.