Hyperproduction of 7-dehydrocholesterol by rewiring the post-squalene module in lipid droplets of Saccharomyces cerevisiae

Xiu, Xiang; Xu, Xianhao; Wu, Yaokang; Liu, Yanfeng; Li, Jianghua; Du, Guocheng; Chen, Jian; Lv, Xueqin; Liu, Long

doi:10.1016/j.ymben.2024.10.001

Metabolic Engineering

2024

DOI: 10.1016/j.ymben.2024.10.001

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Hyperproduction of 7-dehydrocholesterol by rewiring the post-squalene module in lipid droplets of Saccharomyces cerevisiae

Xiang Xiu,

Xianhao Xu,

Yaokang Wu

et al.

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Cited by 3 publications

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Efficient 7-Dehydrocholesterol Production by Multiple Metabolic Engineering of Diploid Saccharomyces cerevisiae

Ye,

Xu,

et al. 2024

J. Agric. Food Chem.

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7-Dehydrocholesterol (7-DHC), a direct precursor of vitamin D3, has attracted increasing attention in microbial fermentation recently. In this study, 7-DHC biosynthesis in diploid Saccharomyces cerevisiae with robust ergosterol production was achieved by heterologous 24-dehydrocholesterol reductase expression, generating 44.1 mg/L 7-DHC, whereas the titer of ergosterol decreased by 40.5%. The ergosterol biosynthetic pathway was completely blocked by knocking out ERG6 and ERG5, affording a 4.2fold increase in the 7-DHC titer. Subsequently, the facilitation of the mevalonate and the postsqualene pathways accompanied by elimination of transcriptional repressors enhanced 7-DHC synthesis, and the 7-DHC titer reached 738.5 mg/L in a shake flask. Further validation in a 50 L fermenter demonstrated that the 7-DHC titer reached 3.80 g/L within just 24 h, with productivity reaching 158.3 mg/L/h, setting a new benchmark as the highest reported to date. This study paves the way toward a large-scale and cost-effective manufacture of 7-DHC.

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Efficient 7-Dehydrocholesterol Production by Multiple Metabolic Engineering of Diploid Saccharomyces cerevisiae

Ye,

Xu,

et al. 2024

J. Agric. Food Chem.

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Multiple Strategies Enhance 7-Dehydrocholesterol Production from Kitchen Waste by Engineered Yarrowia lipolytica

Dong,

Zhou,

Hou

et al. 2024

J. Agric. Food Chem.

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Establishing Komagataella phaffii as a Cell Factory for Efficient Production of Cholesterol Sulfate

Xiao,

Li,

Pan

et al. 2024

ACS Sustainable Chem. Eng.

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Hyperproduction of 7-dehydrocholesterol by rewiring the post-squalene module in lipid droplets of Saccharomyces cerevisiae

Cited by 3 publications

References 39 publications

Efficient 7-Dehydrocholesterol Production by Multiple Metabolic Engineering of Diploid Saccharomyces cerevisiae

Efficient 7-Dehydrocholesterol Production by Multiple Metabolic Engineering of Diploid Saccharomyces cerevisiae

Multiple Strategies Enhance 7-Dehydrocholesterol Production from Kitchen Waste by Engineered Yarrowia lipolytica

Establishing Komagataella phaffii as a Cell Factory for Efficient Production of Cholesterol Sulfate

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