Identification of biosynthetic genes for the β-carboline alkaloid kitasetaline and production of the fluorinated derivatives by heterologous expression
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- Shohei Ueda
- 0000 0004 0373 3971 grid.136593.b International Center for Biotechnology Osaka University 2-1 Yamadaoka 565-0871 Suita Osaka Japan
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- Haruo Ikeda
- 0000 0000 9206 2938 grid.410786.c Kitasato Institute for Life Sciences Kitasato University 1-15-1 Kitasato 252-0373 Sagamihara Kanagawa Japan
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- Takushi Namba
- 0000 0001 0659 9825 grid.278276.e Science Research Center Kochi University Kohasu, Oko-cho 783-8505 Nankoku Kochi Japan
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- Yukinori Ikejiri
- 0000 0004 0373 3971 grid.136593.b International Center for Biotechnology Osaka University 2-1 Yamadaoka 565-0871 Suita Osaka Japan
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- Yuri Nishimoto
- 0000 0004 0373 3971 grid.136593.b International Center for Biotechnology Osaka University 2-1 Yamadaoka 565-0871 Suita Osaka Japan
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- Masayoshi Arai
- 0000 0004 0373 3971 grid.136593.b Graduate School of Pharmaceutical Sciences Osaka University 1-6 Yamadaoka 565-0871 Suita Osaka Japan
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- Takuya Nihira
- 0000 0004 0373 3971 grid.136593.b International Center for Biotechnology Osaka University 2-1 Yamadaoka 565-0871 Suita Osaka Japan
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- Shigeru Kitani
- 0000 0004 0373 3971 grid.136593.b International Center for Biotechnology Osaka University 2-1 Yamadaoka 565-0871 Suita Osaka Japan
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説明
<jats:title>Abstract</jats:title> <jats:p>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.</jats:p>
収録刊行物
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- Journal of Industrial Microbiology and Biotechnology
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Journal of Industrial Microbiology and Biotechnology 46 (5), 739-750, 2019-05-01
Oxford University Press (OUP)
