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Characterization of AvaR1, a butenolide-autoregulator receptor for biosynthesis of a Streptomyces hormone in Streptomyces avermitilis

  • Applied genetics and molecular biotechnology
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Abstract

Streptomyces hormones, sometimes called as autoregulators, are important signaling molecules to trigger secondary metabolism across many Streptomyces species. We recently identified a butenolide-type autoregulator (termed avenolide) as a new class of Streptomyces hormone from Streptomyces avermitilis that produces important anthelmintic agent avermectin. Avenolide triggers the production of avermectin with minimum effective concentration of nanomolar. Here, we describe the characterization of avaR1 encoding an avenolide receptor in the regulation of avermectin production and avenolide biosynthesis. The disruption of avaR1 resulted in transcriptional derepression of avenolide biosynthetic gene with an increase in avenolide production, with no change in the avermectin production profile. Moreover, the avaR1 mutant showed increased transcription of avaR1. Together with clear DNA-binding capacity of AvaR1 toward avaR1 upstream region, it suggests that AvaR1 negatively controls the expression of avaR1 through the direct binding to the promoter region of avaR1. These findings revealed that the avenolide receptor AvaR1 functions as a transcriptional repressor for avenolide biosynthesis and its own synthesis.

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Acknowledgments

This study was performed by S.P.S. in partial fulfillment of the requirements for a Ph.D. This work was supported by a Grant-in-Aid for Scientific Research (C) (No. 15K07358) from the Japan Society for the Promotion of Science (JSPS) to S.K., in part by a Grant-in-Aid for Scientific Research (B) (No. 24310157) from JSPS to T.N. and S.K., and by a scholarship from the Ministry of Education, Culture, Sports, Science, and Technology of Japan to S.P.S.

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  1. Hiroyuki Iguchi

    Present address: Department of Agriculture and Food Technology, Faculty of Bioenvironmental Science, Kyoto Gakuen University, 1-1 Nanjo-Ohtani, Sogabe, Kameoka, Kyoto, 621-8555, Japan

Authors and Affiliations

  1. International Center for Biotechnology, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Suandi Pratama Sultan, Shigeru Kitani, Kiyoko T Miyamoto, Hiroyuki Iguchi, Tokitaka Atago & Takuya Nihira

  2. Kitasato Institute for Life Sciences, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa, 252-0373, Japan

    Haruo Ikeda

  3. MU-OU Collaborative Research Center for Bioscience and Biotechnology, Faculty of Science, Mahidol University, Rama VI Rd, Bangkok, 10400, Thailand

    Takuya Nihira

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  1. Suandi Pratama Sultan
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Correspondence to Takuya Nihira.

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Sultan, S.P., Kitani, S., Miyamoto, K.T. et al. Characterization of AvaR1, a butenolide-autoregulator receptor for biosynthesis of a Streptomyces hormone in Streptomyces avermitilis . Appl Microbiol Biotechnol 100, 9581–9591 (2016). https://doi.org/10.1007/s00253-016-7781-4

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