High-level recombinant production of squalene using selected Saccharomyces cerevisiae strains
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For recombinant production of squalene, which is a triterpenoid compound with increasing industrial applications, in microorganisms generally recognized as safe, we screened Saccharomyces cerevisiae strains to determine their suitability. A strong strain dependence was observed in squalene productivity among Saccharomyces cerevisiae strains upon overexpression of genes important for isoprenoid biosynthesis. In particular, a high level of squalene production (400 ± 45 mg/L) was obtained in shake flasks with the Y2805 strain overexpressing genes encoding a bacterial farnesyl diphosphate synthase (ispA) and a truncated form of hydroxyl-3-methylglutaryl-CoA reductase (tHMG1). Partial inhibition of squalene epoxidase by terbinafine further increased squalene production by up to 1.9-fold (756 ± 36 mg/L). Furthermore, squalene production of 2011 ± 75 or 1026 ± 37 mg/L was obtained from 5-L fed-batch fermentations in the presence or absence of terbinafine supplementation, respectively. These results suggest that the Y2805 strain has potential as a new alternative source of squalene production.
KeywordsSqualene Saccharomyces cerevisiae Metabolic engineering Farnesyl diphosphate synthase HMG-CoA reductase
This research was supported by a Grant from the KRIBB Research Initiative Program and by a National Research Foundation of Korea (NRF) Grant from the Korea government (MSIP) (Grant no. NRF-2016R1A2B4009432). This work was also supported by the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry, and Fisheries (IPET) through the Animal Disease Management Technology Development Program funded by the Ministry of Agriculture, Food, and Rural Affairs (MAFRA; 316043-3).
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Conflict of interest
There are no conflicts of interest to declare.
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