期刊
JOURNAL OF BIOSCIENCE AND BIOENGINEERING
卷 124, 期 6, 页码 611-617出版社
SOC BIOSCIENCE BIOENGINEERING JAPAN
DOI: 10.1016/j.jbiosc.2017.06.014
关键词
Streptomyces avermitilis; Autoregulator receptor; Phthoxazolin A; Cryptic secondary metabolites; Avenolide
资金
- Japan Society for the Promotion of Science [JP15K07358]
- New Chemical Technology Research Encouragement Award from the Japan Association for Chemical Innovation
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
- Grants-in-Aid for Scientific Research [16H06447, 15K07358] Funding Source: KAKEN
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. (C) 2017, The Society for Biotechnology, Japan. All rights reserved.
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