Advances in Biochemistry and Microbial Production of Squalene and Its Derivatives

Abstract

Squalene is a linear triterpene formed via the MVA or MEP biosynthetic pathway and is widely distributed in bacteria, fungi, algae, plants, and animals. Metabolically, squalene is used not only as a precursor in the synthesis of complex secondary metabolites such as sterols, hormones, and vitamins, but also as a carbon source in aerobic and anaerobic fermentation in microorganisms. Owing to the increasing roles of squalene as an antioxidant, anticancer, and anti-inflammatory agent, the demand for this chemical is highly urgent. As a result, with the exception of traditional methods of the isolation of squalene from animals (shark liver oil) and plants, biotechnological methods using microorganisms as producers have afforded increased yield and productivity, but a reduction in progress. In this paper, we first review the biosynthetic routes of squalene and its typical derivatives, particularly the squalene synthase route. Second, typical biotechnological methods for the enhanced production of squalene using microbial cell factories are summarized and classified. Finally, the outline and discussion of the novel trend in the production of squalene with several updated events to 2015 are presented.

Plant Sources, Extraction Methods, and Uses of Squalene

“…is includes fermentation with micro-organisms; however, although these techniques are promising, the reported yields (14.5-160.2 mg/L) have not been sufficient to supply commercial production of squalene, and little mention is made of the costs involved [1,29].…”

“…farnesyl-diphosphate (FPP). Finally, two molecules of farnesyldiphosphate are reduced via enzymatic reaction to form the SQ which continues its path to the biosynthesis of phytosterols [1,10,22,29]. Phytosterols are the products of cascade cyclization of SQ; these mechanisms are activated from ionic species by deprotonation, hydration (Figure 4), or from oxidesqualene activated by the action of triterpene enzymes such as squalene cyclase (SQs) and oxide-squalene cyclase (OSQ) [17,30].…”

“…It is a carbon source in the aerobic and anaerobic fermentation of microorganisms [1,2]. e SQ was discovered by Tsujimoto Mitsumaru in 1916, a Japanese researcher who described the compound as a highly unsaturated molecule, assigning its name to the genus from which was isolated, Squalus spp.…”

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.…”

Overexpression of key enzymes of the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway for improving squalene production in Escherichia coli

“…IPP and DMAPP are condensed to form geranyl diphosphate (GPP) by FPP synthase, and subsequently condensed with another IPP to produce farnesyl diphosphate (FPP). Finally, squalene is biosynthesized by a NADPH-mediated reaction catalyzed by squalene synthase (SQS) using FPP as the substrate (Ghimire et al, 2016) (Figure 1). MEP pathway is a *Corresponding author.…”