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...

Full description

Saved in:
Bibliographic Details
Main Authors: Hye-Seon Hwang, Kwang-Rim Baek, Seung-Oh Seo
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Fermentation
Subjects:
Online Access:https://www.mdpi.com/2311-5637/11/4/214
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850144039425277952
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
collection DOAJ
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
record_format Article
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