The regulation of activity of main mevalonic acid pathway enzymes: Farnesyl diphosphate synthase, 3-hydroxy-3-methylglutaryl-CoA reductase, and squalene synthase in yeast Saccharomyces cerevisiae

The co-regulation of the main mevalonic acid pathway enzymes was investigat ed in the yeast Saccharomyces cerevisiae. It was found that a 6-fold increa se in FPPS activity compared with that of the wild-type strain FL100 did no t cause significant changes in HMG-CoA reductase activity, while the amount s of synthesized dolichols and ergosterol increased by 80 and 32%, respecti vely. The disruption of the SQS gene in the strain grown in the presence of ergosterol repressed the activities of both FPP synthase and HMG-CoA reduc tase to a comparable degree, whereas in the same strain starved for ergoste rol the activity of FPPS was 10-fold higher and HMG-CoA reductase activity was practically unchanged. We show that FPPS is the enzyme that regulates t he how rate of synthesized mevalonic acid pathway products independent of H MG-CoA reductase and SQS. (C) 2000 Academic Press.