Squalene in Camellia oleifera: Biosynthetic Pathways, Regulatory Networks, and Functional Perspectives

Squalene is a triterpene with potent biological activities. Squalene (C₃₀H₅₀) is a linear polyunsaturated hydrocarbon composed of six isoprene units and six carbon-carbon double bonds. It serves as an essential precursor for sterols, steroid hormones, and vitamin D in humans and exhibits antioxidant, anti-tumor, and lipid-regulating properties. In plants, squalene is produced via the mevalonate (MVA) and 2-C-methyl-D-erythritol-4-phosphate (MEP) pathways. The key rate-limiting enzymes in these pathways include 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), farnesyl diphosphate synthase (FPS), and squalene synthase (SQS). Camellia oleifera, a unique woody oil crop native to China, is valued for its high-quality edible oil and as a rich natural source of squalene. This review provides a systematic overview of recent progress in squalene biosynthesis in C. oleifera. It summarizes the structural characteristics and biosynthetic routes. It further elaborates on the multi-level regulatory network modulated by transcription factors (WRKY, bHLH, MYB, and ERF), phytohormones (jasmonic acid, abscisic acid, and gibberellin), and abiotic factors (light and drought). Notably, this review distinguishes earlier foundational studies from recent breakthroughs and integrates emerging progress on squalene's non-canonical functions and pathway crosstalk. It further highlights novel regulatory mechanisms unique to C. oleifera (e.g., CoWRKY15, CoMYB1, and CoMYC2). By bridging molecular regulation with practical breeding and metabolic engineering, this review lays a solid theoretical foundation for cultivating high-squalene C. oleifera varieties. It represents a prominent innovation relative to previously published studies.