Identification of a Lysine Residue Important for the Catalytic Activity of Yeast Farnesyl Diphosphate Synthase

The Saccharomyces cerevisiae ERG20 gene (encoding farnesyl diphosphate synthase) has been subjected to a set of mutations at the catalytic site, at position K254 to determine the in vivo impact. The mutated strains have been shown to exhibit various growth rates, sterol profiles and monoterpenol producing capacities. The results obtained suggest that K at position 254 helps to stabilize one of the three Mg²⁺ forming a bridge between the enzyme and DMAPP, and demonstrate that destabilizing two of the three Mg²⁺ ions, by introducing a double mutation at positions K197 and K254, results in a loss of FPPS activity and a lethal phenotype.