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AveI, an AtrA homolog of Streptomyces avermitilis, controls avermectin and oligomycin production, melanogenesis, and morphological differentiation

  • Applied genetics and molecular biotechnology
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Abstract

Streptomyces avermitilis is well known as the producer of anthelmintic agent avermectins, which are widely used in agriculture, veterinary medicine, and human medicine. aveI encodes a TetR-family regulator, which is the homolog of AtrA. It was reported that deletion of aveI caused enhanced avermectin production. In this study, we investigated the regulatory function of the AveI in S. avermitilis. By binding to the 15-nt palindromic sequence in the promoter regions, AveI directly regulates at least 35 genes. AveI represses avermectin production by directly regulating the transcription of the cluster-situated regulator gene aveR and structural genes aveA1, aveA3, and aveD. AveI represses oligomycin production by repressing the CSR gene olmRII and structural genes olmC. AveI activates melanin biosynthesis by activating the expression of melC1C2 operon. AveI activates morphological differentiation by activating the expression of ssgR and ssgD genes, repressing the expression of wblI gene. Besides, AveI regulates many genes involved in primary metabolism, including substrates transport, the metabolism of amino acids, lipids, and carbohydrates. Therefore, AveI functions as a global regulator in S. avermitilis, controls not only secondary metabolism and morphological differentiation, but also primary metabolism.

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Funding

This study was supported by grants from the National Natural Science Foundation of China (No. 31470190) and the project for Extramural Scientists of the State Key Laboratory of Agrobiotechnology (No. 2019SKLAB6-5).

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Authors and Affiliations

  1. State Key Laboratory of Agrobiotechnology and Key Laboratory of Soil Microbiology, Ministry of Agriculture, College of Biological Sciences, China Agricultural University, Beijing, 100193, China

    Lanjie Liu, Yaqing Cheng, Mengya Lyu, Ying Wen, Jilun Li & Zhi Chen

  2. CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China

    Xuejin Zhao

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  1. Lanjie Liu
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  2. Yaqing Cheng
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  3. Mengya Lyu
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  4. Xuejin Zhao
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  5. Ying Wen
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  6. Jilun Li
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  7. Zhi Chen
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Correspondence to Zhi Chen.

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Liu, L., Cheng, Y., Lyu, M. et al. AveI, an AtrA homolog of Streptomyces avermitilis, controls avermectin and oligomycin production, melanogenesis, and morphological differentiation. Appl Microbiol Biotechnol 103, 8459–8472 (2019). https://doi.org/10.1007/s00253-019-10062-3

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