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Effective production of kojic acid in engineered Aspergillus niger

BACKGROUND: Kojic acid (KA) is a widely used compound in the cosmetic, medical, and food industries, and is typically produced by Aspergillus oryzae. To meet increasing market demand, it is important to optimize KA production through seeking alternatives that are more economic than current A. oryzae...

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Autores principales: Wu, Liu, Zhang, Licheng, Li, Xiaojie, Lv, Ruitong, Cao, Wei, Gao, Weixia, Liu, Jiao, Xie, Zhoujie, Liu, Hao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9969635/
https://www.ncbi.nlm.nih.gov/pubmed/36843006
http://dx.doi.org/10.1186/s12934-023-02038-w
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author Wu, Liu
Zhang, Licheng
Li, Xiaojie
Lv, Ruitong
Cao, Wei
Gao, Weixia
Liu, Jiao
Xie, Zhoujie
Liu, Hao
author_facet Wu, Liu
Zhang, Licheng
Li, Xiaojie
Lv, Ruitong
Cao, Wei
Gao, Weixia
Liu, Jiao
Xie, Zhoujie
Liu, Hao
author_sort Wu, Liu
collection PubMed
description BACKGROUND: Kojic acid (KA) is a widely used compound in the cosmetic, medical, and food industries, and is typically produced by Aspergillus oryzae. To meet increasing market demand, it is important to optimize KA production through seeking alternatives that are more economic than current A. oryzae-based methods. RESULTS: In this study, we achieved the first successful heterologous production of KA in Aspergillus niger, an industrially important fungus that does not naturally produce KA, through the expression of the kojA gene from A. oryzae. Using the resulting KA-producing A. niger strain as a platform, we identified four genes (nrkA, nrkB, nrkC, and nrkD) that negatively regulate KA production. Knocking down nrkA or deleting any of the other three genes resulted in a significant increase in KA production in shaking flask cultivation. The highest KA titer (25.71 g/L) was achieved in a pH controlled batch bioreactor using the kojA overexpression strain with a deletion of nrkC, which showed a 26.7% improvement compared to the KA titer (20.29 g/L) that was achieved in shaking flask cultivation. CONCLUSION: Our study demonstrates the potential of using A. niger as a platform for studying KA biosynthesis and regulation, and for the cost-effective production of KA in industrial strain development. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12934-023-02038-w.
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spelling pubmed-99696352023-02-28 Effective production of kojic acid in engineered Aspergillus niger Wu, Liu Zhang, Licheng Li, Xiaojie Lv, Ruitong Cao, Wei Gao, Weixia Liu, Jiao Xie, Zhoujie Liu, Hao Microb Cell Fact Research BACKGROUND: Kojic acid (KA) is a widely used compound in the cosmetic, medical, and food industries, and is typically produced by Aspergillus oryzae. To meet increasing market demand, it is important to optimize KA production through seeking alternatives that are more economic than current A. oryzae-based methods. RESULTS: In this study, we achieved the first successful heterologous production of KA in Aspergillus niger, an industrially important fungus that does not naturally produce KA, through the expression of the kojA gene from A. oryzae. Using the resulting KA-producing A. niger strain as a platform, we identified four genes (nrkA, nrkB, nrkC, and nrkD) that negatively regulate KA production. Knocking down nrkA or deleting any of the other three genes resulted in a significant increase in KA production in shaking flask cultivation. The highest KA titer (25.71 g/L) was achieved in a pH controlled batch bioreactor using the kojA overexpression strain with a deletion of nrkC, which showed a 26.7% improvement compared to the KA titer (20.29 g/L) that was achieved in shaking flask cultivation. CONCLUSION: Our study demonstrates the potential of using A. niger as a platform for studying KA biosynthesis and regulation, and for the cost-effective production of KA in industrial strain development. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12934-023-02038-w. BioMed Central 2023-02-27 /pmc/articles/PMC9969635/ /pubmed/36843006 http://dx.doi.org/10.1186/s12934-023-02038-w Text en © The Author(s) 2023 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
Wu, Liu
Zhang, Licheng
Li, Xiaojie
Lv, Ruitong
Cao, Wei
Gao, Weixia
Liu, Jiao
Xie, Zhoujie
Liu, Hao
Effective production of kojic acid in engineered Aspergillus niger
title Effective production of kojic acid in engineered Aspergillus niger
title_full Effective production of kojic acid in engineered Aspergillus niger
title_fullStr Effective production of kojic acid in engineered Aspergillus niger
title_full_unstemmed Effective production of kojic acid in engineered Aspergillus niger
title_short Effective production of kojic acid in engineered Aspergillus niger
title_sort effective production of kojic acid in engineered aspergillus niger
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9969635/
https://www.ncbi.nlm.nih.gov/pubmed/36843006
http://dx.doi.org/10.1186/s12934-023-02038-w
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