title: Characterization of AvaR1, a butenolide-autoregulator receptor for biosynthesis of a Streptomyces hormone in Streptomyces avermitilis.
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.
authors.affiliation: International Center for Biotechnology, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Suandi Pratama
authors.initials: SP
authors.lastname: Sultan
authors.affiliation: International Center for Biotechnology, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kitani
authors.affiliation: International Center for Biotechnology, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Kiyoko T
authors.initials: KT
authors.lastname: Miyamoto
authors.affiliation: International Center for Biotechnology, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.|Department of Agriculture and Food Technology, Faculty of Bioenvironmental Science, Kyoto Gakuen University, 1-1 Nanjo-Ohtani, Sogabe, Kameoka, Kyoto, 621-8555, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Iguchi
authors.affiliation: International Center for Biotechnology, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Tokitaka
authors.initials: T
authors.lastname: Atago
authors.affiliation: Kitasato Institute for Life Sciences, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa, 252-0373, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Ikeda
authors.affiliation: International Center for Biotechnology, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan. nihira@icb.osaka-u.ac.jp.|MU-OU Collaborative Research Center for Bioscience and Biotechnology, Faculty of Science, Mahidol University, Rama VI Rd, Bangkok, 10400, Thailand. nihira@icb.osaka-u.ac.jp.
authors.forename: Takuya
authors.initials: T
authors.lastname: Nihira
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D055786:Gene Knockout Techniques; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D011956:Receptors, Cell Surface; D012097:Repressor Proteins; D007559:Ivermectin; C019264:avermectin; C004511:butenolide; D015107:4-Butyrolactone
keywords: Avenolide; Avermectin; Butenolide-type autoregulator; Streptomyces; Streptomyces hormone