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Characterization of a regulatory gene, aveR, for the biosynthesis of avermectin in Streptomyces avermitilis

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Abstract

Avermectin is an important macrocyclic polyketide produced by Streptomyces avermitilis and widely used as an anthelmintic agent in the medical, veterinary, and agricultural fields. The avermectin biosynthetic gene cluster contains aveR, which belongs to the LAL-family of regulatory genes. In this study, aveR was inactivated by gene replacement in the chromosome of S. avermitilis, resulting in the complete loss of avermectin production. The aveR mutant was unable to convert an avermectin intermediate to any avermectin derivatives, and complementation by intact aveR and its proper upstream region restored avermectin production in the mutant, suggesting that AveR is a positive regulator controlling the expression of both polyketide biosynthetic genes and postpolyketide modification genes in avermectin biosynthesis. Despite the general concept that an increased amount of a positive pathway-specific regulator leads to higher production, a higher amount of aveR resulted in complete loss of avermectin, indicating that there is a maximum threshold concentration of aveR for the production of avermectin.

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Acknowledgements

This study was supported in part by grants from the "Research Project in the Field of Biotechnology" under the Ministry of Education, Culture, Sports, Science and Technology of Japan, the National Research Council of Thailand and the National Science and Technology Development Agency of Thailand (to T.N.) and a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS) (No. 20310122 to H.I.).

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Correspondence to Takuya Nihira.

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Kitani, S., Ikeda, H., Sakamoto, T. et al. Characterization of a regulatory gene, aveR, for the biosynthesis of avermectin in Streptomyces avermitilis . Appl Microbiol Biotechnol 82, 1089–1096 (2009). https://doi.org/10.1007/s00253-008-1850-2

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Keywords

  • Avermectin
  • Regulatory gene
  • LAL-family transcriptional regulator