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Characterization of AvaR1, an autoregulator receptor that negatively controls avermectins production in a high avermectin-producing strain

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Abstract

Many γ-butyrolactone-autoregulator receptors control the production of secondary metabolites in Streptomyces spp. Hence, AvaR1, an autoregulator receptor protein in Streptomyces avermitilis, was characterized as a negative regulator of avermectin (Ave) production. Deletion of AvaR1 in a high-producing strain increased production of Ave B1a approx. 1.75 times (~700 μg/ml) compared with the parent strain. Semi-quantitative RT-PCR and electrophoretic mobility shift assays revealed that AvaR1 regulates the biosynthesis of Ave but not through the aveR pathway-specific regulatory gene. A special signaling molecule, avenolide, increased production of Ave. This study has refined our understanding of how avenolide regulates the production of Aves which is promising for developing new methods to improve the production of antibiotics in industrial strains.

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References

  • Alper H, Moxley J, Nevoigt E, Fink GR, Stephanopoulos G (2006) Engineering yeast transcription machinery for improved ethanol tolerance and production. Science 314:1565–1568

    Article  CAS  PubMed  Google Scholar 

  • Bibb MJ (2005) Regulation of secondary metabolism in Streptomycetes. Curr Opin Microbiol 8:208–215

    Article  CAS  PubMed  Google Scholar 

  • Burg RW, Miller BM, Baker EE, Birnbaum J, Currie SA, Hartman R, Kong YL, Monaghan RL, Olson G, Putter I, Tunac JB, Wallick H, Stapley EO, Oiwa R, Omura S (1979) Avermectins, new family of potent anthelmintic agents-producing organism and fermentation. Antimicrob Agents Chemother 15:361–367

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chen L, Lu YH, Chen J, Zhang WW, Shu D, Qin ZJ, Yang S, Jiang WH (2008) Characterization of a negative regulator AveI for avermectin biosynthesis in Streptomyces avermitilis NRRL8165. Appl Microbiol Biotechnol 80:277–286

    Article  CAS  PubMed  Google Scholar 

  • Duong CTP, Lee HN, Choi SS, Lee SY, Kim ES (2009) Functional expression of SAV3818, a putative tetr-family transcriptional regulatory gene from Streptomyces avermitilis, stimulates antibiotic production in Streptomyces species. J Microbiol Biotechnol 19:136–139

    Article  CAS  PubMed  Google Scholar 

  • Egerton JR, Ostlind DA, Blair LS, Eary CH, Suhayda D, Cifelli S, Riek RF, Campbell WC (1979) Avermectins, new family of potent anthelmintic agents-efficacy of the bia component. Antimicrob Agents Chemother 15:372–378

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Horinouchi S (2002) A microbial hormone, A-factor, as a master switch for morphological differentiation and secondary metabolism in Streptomyces griseus. Front Biosci 7:D2045–D2057

    Article  CAS  PubMed  Google Scholar 

  • Ikeda H, Omura S (1997) Avermectin biosynthesis. Chem Rev 97:2591–2609

    Article  CAS  PubMed  Google Scholar 

  • Ikeda H, Nonomiya T, Usami M, Ohta T, Omura S (1999) Organization of the biosynthetic gene cluster for the polyketide anthelmintic macrolide avermectin in Streptomyces avermitilis. Proc Natl Acad Sci USA 96:9509–9514

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kitani S, Ikeda H, Sakamoto T, Noguchi S, Nihira T (2009) Characterization of a regulatory gene, aveR, for the biosynthesis of avermectin in Streptomyces avermitilis. Appl Microbiol Biotechnol 82:1089–1096

    Article  CAS  PubMed  Google Scholar 

  • Kitani S, Miyamoto KT, Takamatsu S, Herawati E, Iguchi H, Nishitomi K, Uchida M, Nagamitsu T, Omura S, Ikeda H, Nihira T (2011) Avenolide, a Streptomyces hormone controlling antibiotic production in Streptomyces avermitilis. Proc Natl Acad Sci USA 108:16410–16415

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Miyamoto KT, Kitani S, Komatsu M, Ikeda H, Nihira T (2011) The autoregulator receptor homologue AvaR3 plays a regulatory role in antibiotic production, mycelial aggregation and colony development of Streptomyces avermitilis. Microbiology 157:2266–2275

    Article  CAS  PubMed  Google Scholar 

  • Natsume R, Ohnishi Y, Senda T, Horinouchi S (2004) Crystal structure of a γ-butyrolactone autoregulator receptor protein in Streptomyces coelicolor A3(2). J Mol Biol 336:409–419

    Article  CAS  PubMed  Google Scholar 

  • Nevoigt E, Fischer C, Mucha O, Matthaeus F, Stahl U, Stephanopoulos G (2007) Engineering promoter regulation. Biotechnol Bioeng 96:550–558

    Article  CAS  PubMed  Google Scholar 

  • Ohnishi Y, Yamazaki H, Kato JY, Tomono A, Horinouchi S (2005) AdpA, a central transcriptional regulator in the A-factor regulatory cascade that leads to morphological development and secondary metabolism in Streptomyces griseus. Biosci Biotechnol Biochem 69:431–439

    Article  CAS  PubMed  Google Scholar 

  • Stephanopoulos G (2007) Challenges in engineering microbes for biofuels production. Science 315:801–804

    Article  CAS  PubMed  Google Scholar 

  • Takano E (2006) γ-Butyrolactones: Streptomyces signalling molecules regulating antibiotic production and differentiation. Curr Opin Microbiol 9:287–294

    Article  CAS  PubMed  Google Scholar 

  • Yang YH, Joo HS, Lee K, Liou KK, Lee HC, Sohng JK, Kim BG (2005) Novel method for detection of butanolides in Streptomyces coelicolor culture broth, using a His-tagged receptor (ScbR) and mass spectrometry. Appl Environ Microbiol 71:5050–5055

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhu DQ, He XY, Zhou XF, Deng ZX (2005) Expression of the melC operon in several Streptomyces strains is positively regulated by AdpA, an AraC family transcriptional regulator involved in morphological development in Streptomyces coelicolor. J Bacteriol 187:3180–3187

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

We thank the grants from National Basic Research Program of China (973 Program) 2009CB118901 and the Chinese Academy of Science for the financial support. We thank the group of Prof. Weihong Jiang for providing the technical help.

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Correspondence to Gong-Li Tang.

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Wang, JB., Zhang, F., Pu, JY. et al. Characterization of AvaR1, an autoregulator receptor that negatively controls avermectins production in a high avermectin-producing strain. Biotechnol Lett 36, 813–819 (2014). https://doi.org/10.1007/s10529-013-1416-y

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  • DOI: https://doi.org/10.1007/s10529-013-1416-y

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