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Effect of Amplifying Deregulated HMG CoA Reductase

Amplification of GGPP Synthase

Amplifying Deregulated HMG CoA Reductase

  

Increasing the level of deregulated HMG CoA reductase enzyme activity was accomplished by over-expressing the catalytic domain of the HMG2 gene. This construct was developed by R. Hampton (Department of Biology, U.C. San Diego), and fuses the region of the HMG2 gene coding for the carboxy-terminal half of the enzyme to the strong GPD promoter. This portion of the gene lacks the transcriptional and protein degradation signals that normally control the level of this enzyme. In shake flask experiments, strains that over-express the deregulated HMG CoA reductase reproducibly exhibited lower farnesol accumulation than strains with normal HMG CoA reductase. However, in fermentors under fed-batch conditions, strains that over-expressed the deregulated HMG CoA reductase accumulated significantly more farnesol than the control strains.