Recent advances in the microbial production of squalene

Abstract

Squalene is a triterpene hydrocarbon, a biochemical precursor for all steroids in plants and animals. It is a principal component of human surface lipids, in particular of sebum. Squalene has several applications in the food, pharmaceutical, and medical sectors. It is essentially used as a dietary supplement, vaccine adjuvant, moisturizer, cardio-protective agent, anti-tumor agent and natural antioxidant. With the increased demand for squalene along with regulations on shark-derived squalene, there is a need to find alternatives for squalene production which are low-cost as well as sustainable. Microbial platforms are being considered as a potential option to meet such challenges. Considerable progress has been made using both wild-type and engineered microbial strains for improved productivity and yields of squalene. Native strains for squalene production are usually limited by low growth rates and lesser titers. Metabolic engineering, which is a rational strain engineering tool, has enabled the development of microbial strains such as Saccharomyces cerevisiae and Yarrowia lipolytica, to overproduce the squalene in high titers. This review focuses on key strain engineering strategies involving both in-silico and in-vitro techniques. Emphasis is made on gene manipulations for improved precursor pool, enzyme modifications, cofactor regeneration, up-regulation of limiting reactions, and downregulation of competing reactions during squalene production. Process strategies and challenges related to both upstream and downstream during mass cultivation are detailed.

Value-Added Squalene in Single-Cell Oil Produced with Cutaneotrichosporon oleaginosus for Food Applications

“…Several studies report that oxygen limitation in anaerobic cultivation can increase squalene yield. , Therefore, the effect of oxygen availability on the squalene concentration in C. oleaginosus biomass was investigated in the 250 mL bioreactor setup (Figure ).…”

“…In addition to being a hormone and vitamin D2 precursor, the triterpenoid squalene is a potent nontoxic antioxidant with a comparably high oral lethal dose in mice of LD 50 = 5 g/kg . Therefore, it has gained attention as a potential food supplement for the prevention of cancer and cardiovascular diseases . Moreover, the cosmetic industry uses it as a moisture-retaining, antioxidant, and emollient agent in biological skin care applications as it naturally accounts for 13% of human sebum .…”

“…9 Further, squalene was in the recent attention of the pharmaceutical industry because of its role in nanoparticle research for drug delivery, specifically due to its relevance as an adjuvant in vaccines like Covid-19 vaccines. 8 Historically, squalene was mainly sourced from deep-sea shark liver oil with a high squalene content of 800−74,500 mg/100 g oil. 10 An overview of squalene sources from different organisms is shown in Table 1.…”

“…Moreover, the cosmetic industry uses it as a moisture-retaining, antioxidant, and emollient agent in biological skin care applications as it naturally accounts for 13% of human sebum . Further, squalene was in the recent attention of the pharmaceutical industry because of its role in nanoparticle research for drug delivery, specifically due to its relevance as an adjuvant in vaccines like Covid-19 vaccines . Historically, squalene was mainly sourced from deep-sea shark liver oil with a high squalene content of 800–74,500 mg/100 g oil .…”

A Comprehensive Review of Health-Benefiting Components in Rapeseed Oil

“…Squalene, as a precursor of other sterols, exists in various vegetable oils. The content differs with the vegetable type, cultivar, agronomic factors, and extraction methods, among others [ 64 , 65 ]. In rapeseed oil, the content of squalene is reported to be approximately 47.8 mg/Kg, which is far less than that in refined olive oil (4784.28 mg/Kg).…”