Lovastatin inhibits the production of gibberellins but not sterol or carotenoid biosynthesis in Gibberella fujikuroi.
Sterols, carotenoids and gibberellins are synthesized after the reduction of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) to mevalonate in different subcellular compartments of the fungus Gibberella fujikuroi. Lovastatin inhibits growth in many organisms, presumably because of the inhibition of the synthesis of essential terpenoids. However, in G. fujikuroi growth of the mycelia and sterol and carotenoid content were not affected by the presence of lovastatin. Nevertheless, lovastatin did inhibit the accumulation of gibberellins in the culture medium; this inhibition, however, was counteracted by the addition of mevalonate to the medium. The conversion of HMG-CoA to mevalonate in cell-free extracts was inhibited by 10 nM lovastatin. Since G. fujikuroi apparently possesses a single gene for HMG-CoA reductase, as shown by Southern hybridization and PCR amplification, it was concluded that the biosynthesis of sterols, carotenoids and gibberellins shares a single HMG-CoA reductase, but the respective subcellular compartments are differentially accessible to lovastatin.
Giordano
W
W
Departamento de Biología Molecular, Universidad Nacional de Río Cuarto, Córdoba, Argentina.
Avalos
J
J
Fernández-Martín
R
R
Cerdá-Olmedo
E
E
Domenech
C E
CE
D000214:Acyl Coenzyme A / Q000378:metabolism; D000595:Amino Acid Sequence; D015139:Blotting, Southern; D002338:Carotenoids / Q000096:biosynthesis*; D004271:DNA, Fungal; D005656:Fungal Proteins; D005874:Gibberella / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D005875:Gibberellins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D008148:Lovastatin / Q000494:pharmacology*; D008798:Mevalonic Acid / Q000494:pharmacology; D008969:Molecular Sequence Data; D020161:Physical Chromosome Mapping; D016133:Polymerase Chain Reaction; D016415:Sequence Alignment; D013261:Sterols / Q000096:biosynthesis*; D013997:Time Factors
D000214:Acyl Coenzyme A; D004271:DNA, Fungal; D005656:Fungal Proteins; D005875:Gibberellins; D013261:Sterols; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D002338:Carotenoids; D008148:Lovastatin; D008798:Mevalonic Acid