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dc.contributor.authorDian Anggraini Surotoen_US
dc.contributor.authorShigeru Kitanien_US
dc.contributor.authorKiyoko T. Miyamotoen_US
dc.contributor.authorYasuko Sakihamaen_US
dc.contributor.authorMasayoshi Araien_US
dc.contributor.authorHaruo Ikedaen_US
dc.contributor.authorTakuya Nihiraen_US
dc.contributor.otherOsaka Universityen_US
dc.contributor.otherHokkaido Universityen_US
dc.contributor.otherKitasato Universityen_US
dc.contributor.otherMahidol Universityen_US
dc.identifier.citationJournal of Bioscience and Bioengineering. Vol.124, No.6 (2017), 611-617en_US
dc.description.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.en_US
dc.rightsMahidol Universityen_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.subjectChemical Engineeringen_US
dc.subjectImmunology and Microbiologyen_US
dc.titleActivation of cryptic phthoxazolin A production in Streptomyces avermitilis by the disruption of autoregulator-receptor homologue AvaR3en_US
Appears in Collections:Scopus 2016-2017

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