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Engineering Saccharomyces cerevisiae for the production of dihydroquercetin from naringenin

BACKGROUND: Dihydroquercetin (DHQ), a powerful bioflavonoid, has a number of health-promoting qualities and shows potential as a treatment for a number of disorders. Dihydroquercetin biosynthesis is a promising solution to meet the rising demand for dihydroquercetin. However, due to the significant...

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Autores principales: Yu, Shiqin, Li, Mingjia, Gao, Song, Zhou, Jingwen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569186/
https://www.ncbi.nlm.nih.gov/pubmed/36243863
http://dx.doi.org/10.1186/s12934-022-01937-8
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author Yu, Shiqin
Li, Mingjia
Gao, Song
Zhou, Jingwen
author_facet Yu, Shiqin
Li, Mingjia
Gao, Song
Zhou, Jingwen
author_sort Yu, Shiqin
collection PubMed
description BACKGROUND: Dihydroquercetin (DHQ), a powerful bioflavonoid, has a number of health-promoting qualities and shows potential as a treatment for a number of disorders. Dihydroquercetin biosynthesis is a promising solution to meet the rising demand for dihydroquercetin. However, due to the significant accumulation of eriodietyol (ERI), naringenin (NAR), dihydrokaempferol (DHK), and other metabolites, the yield of DHQ biosynthesis is low. As a result, this is the hindrance to the biosynthesis of DHQ. RESULTS: In this study, we proposed several strategies to enhance the product formation and reduce the metabolites in accumulation. The flavonoid 3′-hydroxylase (F3′H) and cytochrome P450 reductase from different species were co-expressed in S. cerevisiae, and the best strain expressing the P450-reductase enzyme complex (SmF3′H/ScCPR) yielded 435.7 ± 7.6 mg/L of ERI from NAR in the deepwell microplate. The product conversion rate was improved further by mutating the predicted potential ubiquitination sites to improve SmF3′H stability, resulting in a 12.8% increase in titre using the mutant SmF3′H (K290R). Besides, different F3Hs from various sources and promoters were tested for the improved DHQ production, with the best strain producing 381.2 ± 10.7 mg/L of DHQ from 1 g/L of NAR, suggesting the temporal regulation the expression of F3H is important for maximization the function of F3′H and F3H. CONCLUSION: This study offers effective strategies for improving DHQ production from NAR and could be used as a reference for related research. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12934-022-01937-8.
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spelling pubmed-95691862022-10-16 Engineering Saccharomyces cerevisiae for the production of dihydroquercetin from naringenin Yu, Shiqin Li, Mingjia Gao, Song Zhou, Jingwen Microb Cell Fact Research BACKGROUND: Dihydroquercetin (DHQ), a powerful bioflavonoid, has a number of health-promoting qualities and shows potential as a treatment for a number of disorders. Dihydroquercetin biosynthesis is a promising solution to meet the rising demand for dihydroquercetin. However, due to the significant accumulation of eriodietyol (ERI), naringenin (NAR), dihydrokaempferol (DHK), and other metabolites, the yield of DHQ biosynthesis is low. As a result, this is the hindrance to the biosynthesis of DHQ. RESULTS: In this study, we proposed several strategies to enhance the product formation and reduce the metabolites in accumulation. The flavonoid 3′-hydroxylase (F3′H) and cytochrome P450 reductase from different species were co-expressed in S. cerevisiae, and the best strain expressing the P450-reductase enzyme complex (SmF3′H/ScCPR) yielded 435.7 ± 7.6 mg/L of ERI from NAR in the deepwell microplate. The product conversion rate was improved further by mutating the predicted potential ubiquitination sites to improve SmF3′H stability, resulting in a 12.8% increase in titre using the mutant SmF3′H (K290R). Besides, different F3Hs from various sources and promoters were tested for the improved DHQ production, with the best strain producing 381.2 ± 10.7 mg/L of DHQ from 1 g/L of NAR, suggesting the temporal regulation the expression of F3H is important for maximization the function of F3′H and F3H. CONCLUSION: This study offers effective strategies for improving DHQ production from NAR and could be used as a reference for related research. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12934-022-01937-8. BioMed Central 2022-10-15 /pmc/articles/PMC9569186/ /pubmed/36243863 http://dx.doi.org/10.1186/s12934-022-01937-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Yu, Shiqin
Li, Mingjia
Gao, Song
Zhou, Jingwen
Engineering Saccharomyces cerevisiae for the production of dihydroquercetin from naringenin
title Engineering Saccharomyces cerevisiae for the production of dihydroquercetin from naringenin
title_full Engineering Saccharomyces cerevisiae for the production of dihydroquercetin from naringenin
title_fullStr Engineering Saccharomyces cerevisiae for the production of dihydroquercetin from naringenin
title_full_unstemmed Engineering Saccharomyces cerevisiae for the production of dihydroquercetin from naringenin
title_short Engineering Saccharomyces cerevisiae for the production of dihydroquercetin from naringenin
title_sort engineering saccharomyces cerevisiae for the production of dihydroquercetin from naringenin
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569186/
https://www.ncbi.nlm.nih.gov/pubmed/36243863
http://dx.doi.org/10.1186/s12934-022-01937-8
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