Retinal Production by Precision Fermentation of <i>Saccharomyces cerevisiae</i>
Retinoids, including retinol, retinal, and retinoic acid, are a group of vitamin A derivatives with skin-improving effects. Retinoic acid is highly effective for skin anti-aging but can cause irritation, requiring a prescription. Retinol, a less irritating alternative, needs conversion to retinal an...
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MDPI AG
2025-04-01
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| Series: | Fermentation |
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| author | Hye-Seon Hwang Kwang-Rim Baek Seung-Oh Seo |
| author_facet | Hye-Seon Hwang Kwang-Rim Baek Seung-Oh Seo |
| author_sort | Hye-Seon Hwang |
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| description | Retinoids, including retinol, retinal, and retinoic acid, are a group of vitamin A derivatives with skin-improving effects. Retinoic acid is highly effective for skin anti-aging but can cause irritation, requiring a prescription. Retinol, a less irritating alternative, needs conversion to retinal and then retinoic acid in the skin, whereas direct absorption of retinal enhances efficacy by bypassing this conversion process. This study aimed to produce retinal through precision fermentation using metabolically engineered <i>Saccharomyces cerevisiae</i>. The introduction of heterologous retinal biosynthetic genes and overexpression of the truncated HMG-CoA reductase (<i>tHMG1</i>) and acetyl-CoA acetyltransferase (<i>ERG10</i>) genes in the mevalonate (MVA) pathway increased retinal production up to 10.2 mg/L. At the same time, ethanol was produced as a major byproduct in <i>S. cerevisiae</i>. To address this, a pyruvate decarboxylase (<i>Pdc</i>)-deficient <i>S. cerevisiae</i> strain, incapable of producing ethanol, was employed. Overexpression of <i>ERG10</i> and <i>tHMG1</i> in the <i>Pdc</i>-deficient <i>S. cerevisiae</i> harboring the retinal biosynthetic plasmids achieved a retinal production up to 117.4 mg/L in the dodecane layer without ethanol through a two-phase in situ fermentation and extraction. This study demonstrates that eliminating pyruvate decarboxylase activity effectively redirects carbon flux toward retinal biosynthesis in the recombinant <i>S. cerevisiae</i>, offering a promising approach for sustainable retinal production through precision fermentation. |
| format | Article |
| id | doaj-art-6687b093735e4378b98c03fc1c2cc77e |
| institution | OA Journals |
| issn | 2311-5637 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
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| series | Fermentation |
| spelling | doaj-art-6687b093735e4378b98c03fc1c2cc77e2025-08-20T02:28:28ZengMDPI AGFermentation2311-56372025-04-0111421410.3390/fermentation11040214Retinal Production by Precision Fermentation of <i>Saccharomyces cerevisiae</i>Hye-Seon Hwang0Kwang-Rim Baek1Seung-Oh Seo2Department of Food Science and Biotechnology, Seoul National University of Science and Technology, Seoul 01811, Republic of KoreaDepartment of Food Science and Biotechnology, Seoul National University of Science and Technology, Seoul 01811, Republic of KoreaDepartment of Food Science and Biotechnology, Seoul National University of Science and Technology, Seoul 01811, Republic of KoreaRetinoids, including retinol, retinal, and retinoic acid, are a group of vitamin A derivatives with skin-improving effects. Retinoic acid is highly effective for skin anti-aging but can cause irritation, requiring a prescription. Retinol, a less irritating alternative, needs conversion to retinal and then retinoic acid in the skin, whereas direct absorption of retinal enhances efficacy by bypassing this conversion process. This study aimed to produce retinal through precision fermentation using metabolically engineered <i>Saccharomyces cerevisiae</i>. The introduction of heterologous retinal biosynthetic genes and overexpression of the truncated HMG-CoA reductase (<i>tHMG1</i>) and acetyl-CoA acetyltransferase (<i>ERG10</i>) genes in the mevalonate (MVA) pathway increased retinal production up to 10.2 mg/L. At the same time, ethanol was produced as a major byproduct in <i>S. cerevisiae</i>. To address this, a pyruvate decarboxylase (<i>Pdc</i>)-deficient <i>S. cerevisiae</i> strain, incapable of producing ethanol, was employed. Overexpression of <i>ERG10</i> and <i>tHMG1</i> in the <i>Pdc</i>-deficient <i>S. cerevisiae</i> harboring the retinal biosynthetic plasmids achieved a retinal production up to 117.4 mg/L in the dodecane layer without ethanol through a two-phase in situ fermentation and extraction. This study demonstrates that eliminating pyruvate decarboxylase activity effectively redirects carbon flux toward retinal biosynthesis in the recombinant <i>S. cerevisiae</i>, offering a promising approach for sustainable retinal production through precision fermentation.https://www.mdpi.com/2311-5637/11/4/214<i>Saccharomyces cerevisiae</i>retinalmetabolic engineeringprecision fermentationtwo-phase extraction |
| spellingShingle | Hye-Seon Hwang Kwang-Rim Baek Seung-Oh Seo Retinal Production by Precision Fermentation of <i>Saccharomyces cerevisiae</i> Fermentation <i>Saccharomyces cerevisiae</i> retinal metabolic engineering precision fermentation two-phase extraction |
| title | Retinal Production by Precision Fermentation of <i>Saccharomyces cerevisiae</i> |
| title_full | Retinal Production by Precision Fermentation of <i>Saccharomyces cerevisiae</i> |
| title_fullStr | Retinal Production by Precision Fermentation of <i>Saccharomyces cerevisiae</i> |
| title_full_unstemmed | Retinal Production by Precision Fermentation of <i>Saccharomyces cerevisiae</i> |
| title_short | Retinal Production by Precision Fermentation of <i>Saccharomyces cerevisiae</i> |
| title_sort | retinal production by precision fermentation of i saccharomyces cerevisiae i |
| topic | <i>Saccharomyces cerevisiae</i> retinal metabolic engineering precision fermentation two-phase extraction |
| url | https://www.mdpi.com/2311-5637/11/4/214 |
| work_keys_str_mv | AT hyeseonhwang retinalproductionbyprecisionfermentationofisaccharomycescerevisiaei AT kwangrimbaek retinalproductionbyprecisionfermentationofisaccharomycescerevisiaei AT seungohseo retinalproductionbyprecisionfermentationofisaccharomycescerevisiaei |