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

Abstract

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.

Squalene epoxidase as a target for manipulation of squalene levels in the yeastSaccharomyces cerevisiae

“…Squalene epoxidase (Erg1p) is inhibited by the allylamine antimycotics, for example terbinafine, and this treatment was shown to induce squalene accumulation (Ryder, 1992;Klobu cn ıková et al, 2003;Naziri et al, 2011;Ta et al, 2012). Squalene epoxidase (Erg1p) is inhibited by the allylamine antimycotics, for example terbinafine, and this treatment was shown to induce squalene accumulation (Ryder, 1992;Klobu cn ıková et al, 2003;Naziri et al, 2011;Ta et al, 2012).…”

“…As the first step of squalene metabolism (epoxidation to oxidosqualene) is dependent on molecular oxygen (Jahnke & Klein, 1983), squalene accumulates in cells grown under anaerobic conditions (David & Kirshop, 1973). Suitability of squalene epoxidase encoded by the gene ERG1 as the target for manipulation of squalene levels in yeast was demonstrated by the accumulation of squalene in cells treated by the specific squalene epoxidase inhibitorthe antimycotic terbinafine (Ryder, 1992;Klobu cn ıková et al, 2003;Naziri et al, 2011;Ta et al, 2012). Oxidosqualene cyclase and lanosterol demethylase encoded by the ERG7 and ERG11 genes, respectively, represent other possible targets for manipulation of squalene content.…”

Overproduction of squalene synergistically downregulates ethanol production in Saccharomyces cerevisiae

“…cerevisiae can accommodate itself in industrial processes with remarkable ease; therefore, it is a preferred species among the squalene and ethanol producing strains, (Naziri E, 2011;Spanova M, 2011). Hydroxymethylglutaryl CoA (HMG1) reductase catalyzes the rate limiting step of the squalene biosynthesis pathway and its overexpression has been reported to enhance the production of squalene in S. cerevisiae (Farhi M, 2011;Donal KA, 1997;Paddon CJ, 2013).…”

Correlation of Predictor Variables to Squalene Content in Olive Fruits Using Multivariate Statistical Analysis

“…5,6,7 A number of various studies indicate that squalene has important pharmaceutical activity like preventation cardiovascular diseases, strengthen the immune system, interference many cancer types, improving antitumor action of chemotherapeutic agents, protection the skin by scavenging singlet oxygen generated by UV light, anti-aging, reducing blood cholesterol, inhibition the development of tumors. [5][6][7][8]9,10 The olive oil contains about 0.2-0.7 % squalene. Humans absorbs 60 % of squalene from food and the average intake of squalene is 30 mg/day.…”