Identification and Characterization of the Streptazone E Biosynthetic Gene Cluster in Streptomyces sp. MSC090213JE08 |
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| Authors: | Shoto Ohno Dr Yohei Katsuyama Yuka Tajima Dr Miho Izumikawa Dr Motoki Takagi Dr Manabu Fujie Dr Noriyuki Satoh Dr Kazuo Shin‐ya Dr Yasuo Ohnishi |
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| Affiliation: | 1. Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan;2. Japan Biological Informatics Consortium (JBIC), Koto-ku, Tokyo, Japan;3. Okinawa Institute of Science and Technology Graduate University, Onna-son, Kunigami-gun, Okinawa, Japan;4. National Institute of Advanced Industrial Science and Technology (AIST), Koto-ku, Tokyo, Japan |
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| Abstract: | Streptazone derivatives isolated from Streptomyces species are piperidine alkaloids with a cyclopentab]pyridine scaffold. Previous studies indicated that these compounds are polyketides, but the biosynthetic enzymes responsible for their synthesis are unknown. Here, we have identified the streptazone E biosynthetic gene cluster in Streptomyces sp. MSC090213JE08, which encodes a modular type I PKS and tailoring enzymes that include an aminotransferase, three oxidoreductases, and two putative cyclases. The functions of the six tailoring enzymes were analyzed by gene disruption, and two putative biosynthetic intermediates that accumulated in particular mutants were structurally elucidated. On the basis of these results, we propose a pathway for the biosynthesis of streptazone E in which the two putative cyclases of the nuclear transport factor 2–like superfamily are responsible for C?C bond formation coupled with epoxide ring opening to give the five‐membered ring of streptazone E. |
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| Keywords: | biosynthesis cyclases polyketides streptazone E Streptomyces |
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