Enhanced Squalene Production by Wild-Type Saccharomyces cerevisiae Strains Using Safe Chemical Means

摘要

Interest is increasing in establishing renewable sources for squalene, a functional lipid, as the conventional ones are limited. In the present study, squalene production was achieved in a wild-type laboratory Saccharomyces cerevisiae strain by two safe chemical means using terbinafine (0,05—0.55 mM) and methyl jasmonate (MJ) (0—1.00 mM). Bioprocess kinetics optimized by response surface methodology and monitored by high-performance liquid chromatography revealed a clear dependence of growth and squalene content (SQC) and yield (SQY) on the above regulators. Maximum SQC (10.02 ± 0.53 mg/g dry biomass) and SQY (20.70 ± 1.00 mg/L) were achieved using 0.442 mM terbinafine plus 0.044 mM MJ after 28 h and 0.300 mM terbinafine after 30 h, respectively. A 10-fold increase in SQY was achieved in comparison to that in the absence of regulator. The ruggedness of optimum conditions for SQY was verified for five industrial strains. The cellular lipid fraction (～12% of dry biomass) was rich in squalene (12—13%). Results are encouraging toward bioprocess scale up.