Identification of biosynthetic genes for the β-carboline alkaloid kitasetaline and production of the fluorinated derivatives by heterologous expression
© 2019, Society for Industrial Microbiology and Biotechnology. β-Carboline alkaloids exhibit a broad spectrum of pharmacological and biological activities and are widely distributed in nature. Genetic information on the biosynthetic mechanism of β-carboline alkaloids has not been accumulated in bact...
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| Main Authors: | , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Published: |
2020
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| Subjects: | |
| Online Access: | https://repository.li.mahidol.ac.th/handle/123456789/50180 |
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| Institution: | Mahidol University |
| Summary: | © 2019, Society for Industrial Microbiology and Biotechnology. β-Carboline alkaloids exhibit a broad spectrum of pharmacological and biological activities and are widely distributed in nature. Genetic information on the biosynthetic mechanism of β-carboline alkaloids has not been accumulated in bacteria, because there are only a few reports on the microbial β-carboline compounds. We previously isolated kitasetaline, a mercapturic acid derivative of a β-carboline compound, from the genetically modified Kitasatospora setae strain and found a plausible biosynthetic gene cluster for kitasetaline. Here, we identified and characterized three kitasetaline (ksl) biosynthetic genes for the formation of the β-carboline core structure and a gene encoding mycothiol-S-conjugate amidase for the modification of the N-acetylcysteine moiety by using heterologous expression. The proposed model of kitasetaline biosynthesis shows unique enzymatic systems for β-carboline alkaloids. In addition, feeding fluorotryptophan to the heterologous Streptomyces hosts expressing the ksl genes led to the generation of unnatural β-carboline alkaloids exerting novel/potentiated bioactivities. |
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