Shohei UedaHaruo IkedaTakushi NambaYukinori IkejiriYuri NishimotoMasayoshi AraiTakuya NihiraShigeru KitaniOsaka UniversityKochi UniversityMahidol UniversityKitasato University2020-01-272020-01-272019-05-10Journal of Industrial Microbiology and Biotechnology. Vol.46, No.5 (2019), 739-75014765535136754352-s2.0-85061842685https://repository.li.mahidol.ac.th/handle/20.500.14594/50180© 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.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyChemical EngineeringImmunology and MicrobiologyArticleSCOPUS10.1007/s10295-019-02151-z