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Identification of biosynthetic genes for the β-carboline alkaloid kitasetaline and production of the fluorinated derivatives by heterologous expression

  • Genetics and Molecular Biology of Industrial Organisms - Original Paper
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Journal of Industrial Microbiology & Biotechnology

Abstract

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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Acknowledgements

This work was supported by a Grant-in-Aid for Scientific Research (C) (Grant number 18K05390) from the Japan Society for the Promotion of Science (JSPS) to S.K., by a Grant-in-Aid for Scientific Research on Innovative Areas (Grant number 18H04618) from JSPS to S.K., and by a New Chemical Technology Research Encouragement Award from the Japan Association for Chemical Innovation to S.K.

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Correspondence to Shigeru Kitani.

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This research was conducted by Shohei Ueda in partial fulfillment of the requirements for a Ph.D.

Takuya Nihira: Deceased 17 September 2018.

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Ueda, S., Ikeda, H., Namba, T. et al. Identification of biosynthetic genes for the β-carboline alkaloid kitasetaline and production of the fluorinated derivatives by heterologous expression. J Ind Microbiol Biotechnol 46, 739–750 (2019). https://doi.org/10.1007/s10295-019-02151-z

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