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Characterization of a negative regulator AveI for avermectin biosynthesis in Streptomyces avermitilis NRRL8165

Abstract

A transcriptional activator for actinorhodin biosynthesis, AtrA, was previously characterized in Streptomyces coelicolor A3(2), and an orthologue of atrA, named aveI, is identified in the Streptomyces avermitilis NRRL8165 genome (Uguru et al., Mol Microbiol, 58:131–150, 2005). In this study, genetic and functional characterization of aveI gene was reported. Deletion of aveI gene led to increased biosynthesis of avermectin B1a by about 16-fold. The increased synthesis of avermectin B1a was suppressed by complementation with either aveI gene or its orthologue gene atrA from S. coelicolor, suggesting AveI and AtrA shared the similar functionality and were negative regulators for avermectin biosynthesis in S. avermitilis. However, when aveI was introduced into S. coelicolor on a multi-copy plasmid, the production of actinorhodin was significantly increased, indicating that aveI had a positive effect on actinorhodin biosynthesis in S. coelicolor, the same as its orthologue atrA. Electrophoretic mobility shift assays revealed AveI can bind specifically to the promoter region of actII-ORF4 in vitro but not that of aveR. Although its mechanism still needs to be defined, the species-differential regulation by the same regulator may represent an example of the evolutional strategy that enables bacteria to adapt the existing molecular machinery to a variety of functionalities for growth and survival.

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Acknowledgements

We thank Haiyang Xia for offering the genomic library of S. avermitilis NRRL8165 and Zhejiang Shenghua Biok Biological (China) for offering the medium components for avermectin fermentation. This work was supported by National Natural Science Foundation of China (30770023), the Knowledge Innovation Program of the Chinese Academy of Sciences, KSCX2-SW-329-3, KSCX2-YW-G-007, and National Basic Research Program of China (2007CB707803).

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Correspondence to Weihong Jiang.

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Chen, L., Lu, Y., Chen, J. et al. Characterization of a negative regulator AveI for avermectin biosynthesis in Streptomyces avermitilis NRRL8165. Appl Microbiol Biotechnol 80, 277 (2008). https://doi.org/10.1007/s00253-008-1545-8

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Keywords

  • Avermectin biosynthesis
  • Negative regulator
  • Streptomyces avermitilis
  • Streptomyces coelicolor