Enhancement of farnesyl diphosphate pool as direct precursor of sesquiterpenes through metabolic engineering of the mevalonate pathway in Saccharomyces cerevisiae

摘要: The mevalonate pathway in the yeast Saccharomyces cerevisiae was deregulated order to enhance intracellular pool of farnesyl diphosphate (FPP), direct precursor for biosynthesis sesquiterpenes. Over-expression catalytic domain HMG1, both from genome and plasmid, resulted higher production cubebol, a plant originating sesquiterpene, increased squalene accumulation. Down-regulation ERG9 by replacing its native promoter with regulatable MET3 promoter, enhanced cubebol titers but simultaneous over-expression tHMG1 repression did not further improve production. Furtheremore, concentrations ergosterol were measured engineered strains. Unexpectedly, significant accumulation restoring observed repressed strains transformed plasmids harboring synthase gene. This could be explained toxicity effect possibly resulting transcription levels genes under control which lead ergosterol.