Fosmidomycin as an inhibitor of the non-mevalonate terpenoid pathway depresses synthesis of secondary carotenoids in flagellates of the green alga Haematococcus pluvialis

The volvocalean microalga Haematococcus pluvialis accumulates secondary car otenoids, mostly astaxanthin and its mono- and di-esters, outside the chlor oplast in lipid vesicles. To elucidate the biosynthetic pathway of this pro cess further, inhibitors of early steps in the terpenoid pathway were appli ed: fosmidomycin as an inhibitor of the 1-deoxy-D-xylulose-5-phosphate redu ctoisomerase in the non-mevalonate branch of the pathway, and mevinolin as a blocker of the 3-hydroxy-3-methylglutaryl-coenzym A reductase in the acet ate/mevalonate branch. Synthesis of secondary carotenoids in the flagellate developmental state of the green alga was induced by nitrate deprivation a nd an increase in cultivation irradiance, and the effects of the inhibitors on growth and the pigment pattern were studied spectrophotometrically and by high performance liquid chromatography. Fosmidomycin at a concentration of 50 mu M reduced synthesis of secondary carotenoids to 50 % of the contro l level after four days of exposure, whereas mevinolin did not exert any ef fect up to a concentration of 200 mu M. We conclude that synthesis of secon dary carotenoids in flagellates of H. pluvialis occurs via the non-mevalona te pathway of terpenoid biosynthesis.