Drastic changes in the substrate specificity of geranylgeranyl diphosphate synthase from Sulfolobus acidocaldarius by a single amino acid substitution

Geranylgeranyl diphosphate (GGPP) synthase catalyzes the condensation of isopentenyl diphosphate with dimethylallyl diphosphate, geranyl diphosphate or farnesyl diphosphate to produce GGPP as the final product. GGPP synthase in the thermophilic bacterium Sulfolobus acidocaldarius can hardly accept substrate analogs possessing oxygen atoms in their prenyl chains. We have prepared several point-mutated S. acidocaldarius GGPP synthases in which phenylalanine was substituted with glycine (F77G) or serine (F77S). Interestingly, the reactivity of the mutated GGPP synthase was enhanced with respect to substrate analogs possessing ω-oxygen atoms in their prenyl chains.