Metabolic Engineering of Yeasts for the Production of the Triterpene Squalene: Current Status and Future Prospective
Review article, 2025
Squalene, a linear triterpene compound characterized by its distinctive isoprenoid backbone with six transisoprene units, is widely used in the medicinal, nutraceutical, and cosmetic industries. The escalating global demand for squalene, coupled with growing ethical concerns over shark-derived sources and the inherent limitations of plant extraction (low yield) and chemical synthesis (environmental burden), has propelled microbial biosynthesis as a sustainable alternative. While substantial progress has been made in elucidating the mevalonate pathway and regulatory mechanisms of squalene biosynthesis, achieving industrially viable titers through microbial platforms remains an unresolved challenge. This review systematically summarizes recent advances in squalene biosynthesis using yeast chassis, with a focus on metabolic engineering strategies implemented in Saccharomyces cerevisiae and Yarrowia lipolytica. Furthermore, we elaborated on how squalene yields a diverse array of downstream derivatives through intricate enzymatic reactions. These derivatives—including triterpenoid saponins, triterpenoid acids, and steroids—exhibit significant applications in the pharmaceutical, nutraceutical, and cosmetic sectors. By integrating systems metabolic engineering with emerging synthetic biology tools, this work provides a roadmap for advancing strain engineering toward economically feasible squalene biomanufacturing.
metabolic engineering
squalene
Yarrowia lipolytica
microbial synthesis
Saccharomyces cerevisiae
application
Author
Shasha Zuo
Hunan Agricultural Product Processing Institute
Hunan Academy of Agricultural Sciences
Hunan University
Xinjia Tan
Hunan University
Hunan Agricultural Product Processing Institute
Hunan Academy of Agricultural Sciences
Jiwei Mao
Chalmers, Life Sciences, Systems and Synthetic Biology
Fanglin Hu
Hunan University
Hunan Agricultural Product Processing Institute
Hunan Academy of Agricultural Sciences
Jiaxu Chen
Hunan Academy of Agricultural Sciences
Hunan Agricultural Product Processing Institute
China Agricultural University
Liusha Fan
Hunan Academy of Agricultural Sciences
Hunan University
Hunan Agricultural Product Processing Institute
Qiyuan Lu
Hunan Agricultural Product Processing Institute
Hunan Academy of Agricultural Sciences
Hunan University
Yifei Zhao
Hunan Agricultural Product Processing Institute
Hunan University
Hunan Academy of Agricultural Sciences
Yongtong Wang
Hunan Agricultural Product Processing Institute
Hunan Academy of Agricultural Sciences
Hunan University
Zhiqiang Xiao
Hunan Academy of Agricultural Sciences
Hunan Agricultural Product Processing Institute
Siqi Zhang
Hunan University
Hunan Agricultural Product Processing Institute
Hunan Academy of Agricultural Sciences
Yang Shan
Hunan Academy of Agricultural Sciences
Hunan Agricultural Product Processing Institute
Hunan University
Juan Liu
Hunan Academy of Agricultural Sciences
Hunan Agricultural Product Processing Institute
Fuhua Fu
Hunan Academy of Agricultural Sciences
Hunan Agricultural Product Processing Institute
Hunan University
Microorganisms
20762607 (eISSN)
Vol. 13 11 2422Subject Categories (SSIF 2025)
Molecular Biology
Bioprocess Technology
DOI
10.3390/microorganisms13112422
PubMed
41304107