Biosynthesis of melatonin from l-tryptophan by an engineered microbial cell factory
Abstract Background The demand for melatonin is increasing due to its health-promoting bioactivities such as antioxidant and sleep benefits. Although melatonin is present in various organisms, its low content and high extraction cost make it unsustainable. Biosynthesis is a promising alternative met...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Biotechnology for Biofuels and Bioproducts |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13068-024-02476-7 |
| _version_ | 1797275514842382336 |
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| author | Lijuan Wang Yongdong Deng Jianjie Gao Bo Wang Hongjuan Han Zhenjun Li Wenhui Zhang Yu Wang Xiaoyan Fu Rihe Peng Quanhong Yao Yongsheng Tian Jing Xu |
| author_facet | Lijuan Wang Yongdong Deng Jianjie Gao Bo Wang Hongjuan Han Zhenjun Li Wenhui Zhang Yu Wang Xiaoyan Fu Rihe Peng Quanhong Yao Yongsheng Tian Jing Xu |
| author_sort | Lijuan Wang |
| collection | DOAJ |
| description | Abstract Background The demand for melatonin is increasing due to its health-promoting bioactivities such as antioxidant and sleep benefits. Although melatonin is present in various organisms, its low content and high extraction cost make it unsustainable. Biosynthesis is a promising alternative method for melatonin production. However, the ectopic production of melatonin in microorganisms is very difficult due to the low or insoluble expression of melatonin synthesis genes. Hence, we aim to explore the biosynthesis of melatonin using Escherichia coli as a cell factory and ways to simultaneously coordinated express genes from different melatonin synthesis pathways. Results In this study, the mXcP4H gene from Xanthomonas campestris, as well as the HsAADC, HsAANAT and HIOMT genes from human melatonin synthesis pathway were optimized and introduced into E. coli via a multi-monocistronic vector. The obtained strain BL7992 successfully synthesized 1.13 mg/L melatonin by utilizing L-tryptophan (l-Trp) as a substrate in a shake flask. It was determined that the rate-limiting enzyme for melatonin synthesis is the arylalkylamine N-acetyltransferase, which is encoded by the HsAANAT gene. Targeted metabolomics analysis of l-Trp revealed that the majority of l-Trp flowed to the indole pathway in BL7992, and knockout of the tnaA gene may be beneficial for increasing melatonin production. Conclusions A metabolic engineering approach was adopted and melatonin was successfully synthesized from low-cost l-Trp in E. coli. This study provides a rapid and economical strategy for the synthesis of melatonin. |
| first_indexed | 2024-03-07T15:15:33Z |
| format | Article |
| id | doaj.art-de014830d58743d6a600dec8fd8a1fea |
| institution | Directory Open Access Journal |
| issn | 2731-3654 |
| language | English |
| last_indexed | 2024-03-07T15:15:33Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Biotechnology for Biofuels and Bioproducts |
| spelling | doaj.art-de014830d58743d6a600dec8fd8a1fea2024-03-05T17:57:53ZengBMCBiotechnology for Biofuels and Bioproducts2731-36542024-02-0117111010.1186/s13068-024-02476-7Biosynthesis of melatonin from l-tryptophan by an engineered microbial cell factoryLijuan Wang0Yongdong Deng1Jianjie Gao2Bo Wang3Hongjuan Han4Zhenjun Li5Wenhui Zhang6Yu Wang7Xiaoyan Fu8Rihe Peng9Quanhong Yao10Yongsheng Tian11Jing Xu12Shanghai Key Laboratory of Agricultural Genetics and Breeding, Biotechnology Research Institute of Shanghai Academy of Agricultural SciencesShanghai Key Laboratory of Agricultural Genetics and Breeding, Biotechnology Research Institute of Shanghai Academy of Agricultural SciencesShanghai Key Laboratory of Agricultural Genetics and Breeding, Biotechnology Research Institute of Shanghai Academy of Agricultural SciencesShanghai Key Laboratory of Agricultural Genetics and Breeding, Biotechnology Research Institute of Shanghai Academy of Agricultural SciencesShanghai Key Laboratory of Agricultural Genetics and Breeding, Biotechnology Research Institute of Shanghai Academy of Agricultural SciencesShanghai Key Laboratory of Agricultural Genetics and Breeding, Biotechnology Research Institute of Shanghai Academy of Agricultural SciencesShanghai Key Laboratory of Agricultural Genetics and Breeding, Biotechnology Research Institute of Shanghai Academy of Agricultural SciencesShanghai Key Laboratory of Agricultural Genetics and Breeding, Biotechnology Research Institute of Shanghai Academy of Agricultural SciencesShanghai Key Laboratory of Agricultural Genetics and Breeding, Biotechnology Research Institute of Shanghai Academy of Agricultural SciencesShanghai Key Laboratory of Agricultural Genetics and Breeding, Biotechnology Research Institute of Shanghai Academy of Agricultural SciencesShanghai Key Laboratory of Agricultural Genetics and Breeding, Biotechnology Research Institute of Shanghai Academy of Agricultural SciencesShanghai Key Laboratory of Agricultural Genetics and Breeding, Biotechnology Research Institute of Shanghai Academy of Agricultural SciencesShanghai Key Laboratory of Agricultural Genetics and Breeding, Biotechnology Research Institute of Shanghai Academy of Agricultural SciencesAbstract Background The demand for melatonin is increasing due to its health-promoting bioactivities such as antioxidant and sleep benefits. Although melatonin is present in various organisms, its low content and high extraction cost make it unsustainable. Biosynthesis is a promising alternative method for melatonin production. However, the ectopic production of melatonin in microorganisms is very difficult due to the low or insoluble expression of melatonin synthesis genes. Hence, we aim to explore the biosynthesis of melatonin using Escherichia coli as a cell factory and ways to simultaneously coordinated express genes from different melatonin synthesis pathways. Results In this study, the mXcP4H gene from Xanthomonas campestris, as well as the HsAADC, HsAANAT and HIOMT genes from human melatonin synthesis pathway were optimized and introduced into E. coli via a multi-monocistronic vector. The obtained strain BL7992 successfully synthesized 1.13 mg/L melatonin by utilizing L-tryptophan (l-Trp) as a substrate in a shake flask. It was determined that the rate-limiting enzyme for melatonin synthesis is the arylalkylamine N-acetyltransferase, which is encoded by the HsAANAT gene. Targeted metabolomics analysis of l-Trp revealed that the majority of l-Trp flowed to the indole pathway in BL7992, and knockout of the tnaA gene may be beneficial for increasing melatonin production. Conclusions A metabolic engineering approach was adopted and melatonin was successfully synthesized from low-cost l-Trp in E. coli. This study provides a rapid and economical strategy for the synthesis of melatonin.https://doi.org/10.1186/s13068-024-02476-7BiosynthesisMelatoninl-Tryptophan (l-Trp)Escherichia coliMetabolic engineering |
| spellingShingle | Lijuan Wang Yongdong Deng Jianjie Gao Bo Wang Hongjuan Han Zhenjun Li Wenhui Zhang Yu Wang Xiaoyan Fu Rihe Peng Quanhong Yao Yongsheng Tian Jing Xu Biosynthesis of melatonin from l-tryptophan by an engineered microbial cell factory Biotechnology for Biofuels and Bioproducts Biosynthesis Melatonin l-Tryptophan (l-Trp) Escherichia coli Metabolic engineering |
| title | Biosynthesis of melatonin from l-tryptophan by an engineered microbial cell factory |
| title_full | Biosynthesis of melatonin from l-tryptophan by an engineered microbial cell factory |
| title_fullStr | Biosynthesis of melatonin from l-tryptophan by an engineered microbial cell factory |
| title_full_unstemmed | Biosynthesis of melatonin from l-tryptophan by an engineered microbial cell factory |
| title_short | Biosynthesis of melatonin from l-tryptophan by an engineered microbial cell factory |
| title_sort | biosynthesis of melatonin from l tryptophan by an engineered microbial cell factory |
| topic | Biosynthesis Melatonin l-Tryptophan (l-Trp) Escherichia coli Metabolic engineering |
| url | https://doi.org/10.1186/s13068-024-02476-7 |
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