Effective production of kojic acid in engineered Aspergillus niger
Abstract 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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | Microbial Cell Factories |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12934-023-02038-w |
| _version_ | 1797863218844008448 |
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| author | Liu Wu Licheng Zhang Xiaojie Li Ruitong Lv Wei Cao Weixia Gao Jiao Liu Zhoujie Xie Hao Liu |
| author_facet | Liu Wu Licheng Zhang Xiaojie Li Ruitong Lv Wei Cao Weixia Gao Jiao Liu Zhoujie Xie Hao Liu |
| author_sort | Liu Wu |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-09T22:32:03Z |
| format | Article |
| id | doaj.art-bd312c90245c4bda942712d81b445bea |
| institution | Directory Open Access Journal |
| issn | 1475-2859 |
| language | English |
| last_indexed | 2024-04-09T22:32:03Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbial Cell Factories |
| spelling | doaj.art-bd312c90245c4bda942712d81b445bea2023-03-22T12:43:34ZengBMCMicrobial Cell Factories1475-28592023-02-0122111410.1186/s12934-023-02038-wEffective production of kojic acid in engineered Aspergillus nigerLiu Wu0Licheng Zhang1Xiaojie Li2Ruitong Lv3Wei Cao4Weixia Gao5Jiao Liu6Zhoujie Xie7Hao Liu8MOE Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science & TechnologyMOE Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science & TechnologyMOE Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science & TechnologyMOE Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science & TechnologyMOE Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science & TechnologyMOE Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science & TechnologyMOE Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science & TechnologyMOE Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science & TechnologyMOE Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science & TechnologyAbstract 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.https://doi.org/10.1186/s12934-023-02038-wKojic acidAspergillus nigerHeterologous expressionNegative regulator |
| spellingShingle | Liu Wu Licheng Zhang Xiaojie Li Ruitong Lv Wei Cao Weixia Gao Jiao Liu Zhoujie Xie Hao Liu Effective production of kojic acid in engineered Aspergillus niger Microbial Cell Factories Kojic acid Aspergillus niger Heterologous expression Negative regulator |
| 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 | Kojic acid Aspergillus niger Heterologous expression Negative regulator |
| url | https://doi.org/10.1186/s12934-023-02038-w |
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