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Title: Activation of cryptic phthoxazolin A production in Streptomyces avermitilis by the disruption of autoregulator-receptor homologue AvaR3
Authors: Dian Anggraini Suroto
Shigeru Kitani
Kiyoko T. Miyamoto
Yasuko Sakihama
Masayoshi Arai
Haruo Ikeda
Takuya Nihira
Osaka University
Hokkaido University
Kitasato University
Mahidol University
Keywords: Biochemistry, Genetics and Molecular Biology;Chemical Engineering;Immunology and Microbiology
Issue Date: 1-Dec-2017
Citation: Journal of Bioscience and Bioengineering. Vol.124, No.6 (2017), 611-617
Abstract: © 2017 The Society for Biotechnology, Japan The genomes of actinomycetes encode many cryptic novel/useful bioactive compounds, but access to these cryptic secondary metabolites remains limited. Streptomyces avermitilis predominantly produces three polyketide antibiotics (avermectin, filipin, and oligomycin) but has the potential to produce more secondary metabolites based on the number of cryptic biosynthetic gene clusters. Here, we extensively investigated the metabolite profiles of a gene disruptant of AvaR3 (an autoregulator receptor homologue), which is involved in the pleiotropic regulation of antibiotic production and cell morphology. Unlike the wild-type strain, the avaR3 mutant accumulated compound 3 in the culture. The chemical structure of compound 3 was elucidated on the basis of various spectroscopic analyses, and was identified as phthoxazolin A, a cellulose synthesis inhibitor. Bioassays demonstrated that compound 3 exerts growth inhibitory activity against a broad range of plant pathogenic oomycetes. Moreover, unlike avermectin production, phthoxazolin A (3) production was negatively controlled by avenolide, a new type of autoregulator in streptomycetes, through the function of AvaR3. These results suggest that the genetic manipulation of autoregulator receptor homologues would be a valuable tool for the discovery of cryptic bioactive compounds.
ISSN: 13474421
Appears in Collections:Scopus 2016-2017

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