ArticlePloS one2014
Two adjacent and similar TetR family transcriptional regulator genes, SAV577 and SAV576, co-regulate avermectin production in Streptomyces avermitilis.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 19 citations in OpenAlex.
- Sustainable metabolic engineering requires a perfect trifecta.Current opinion in biotechnology · 2023Review
- Transcriptome-guided identification of a four-component system, SbrH1-R, that modulates milbemycin biosynthesis by influencing gene cluster expression, precursor supply, and antibiotic efflux.Synthetic and systems biotechnology · 2022Article
- AccR, a TetR Family Transcriptional Repressor, Coordinates Short-Chain Acyl Coenzyme A Homeostasis inApplied and environmental microbiology · 2020Article
- SAV4189, a MarR-Family Regulator inFrontiers in microbiology · 2018Article
- SAV742, a Novel AraC-Family Regulator from Streptomyces avermitilis, Controls Avermectin Biosynthesis, Cell Growth and Development.Scientific reports · 2016Article
- Interrogation ofSynthetic and systems biotechnology · 2016Article
- Elucidating the molecular physiology of lantibiotic NAI-107 production in Microbispora ATCC-PTA-5024.BMC genomics · 2016Article
- Increasing Avermectin Production in Streptomyces avermitilis by Manipulating the Expression of a Novel TetR-Family Regulator and Its Target Gene Product.Applied and environmental microbiology · 2015Article
- Dissecting and engineering of the TetR family regulator SACE_7301 for enhanced erythromycin production in Saccharopolyspora erythraea.Microbial cell factories · 2014Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Streptomyces avermitilis is an important bacterial species used for industrial production of avermectins, a family of broad-spectrum anthelmintic agents. We previously identified the protein SAV576, a TetR family transcriptional regulator (TFR), as a downregulator of avermectin biosynthesis that acts by controlling transcription of its major target gene SAV575 (which encodes cytochrome P450/NADPH-ferrihemoprotein reductase) and ave genes. SAV577, another TFR gene, encodes a SAV577 protein that displays high amino acid homology with SAV576. In this study, we examined the effect of SAV577 on avermectin production and the relationships between SAV576 and SAV577. SAV577 downregulated avermectin biosynthesis indirectly, similarly to SAV576. SAV576 and SAV577 both directly repressed SAV575 transcription, and reciprocally repressed each other's expression. SAV575 transcription levels in various S. avermitilis strains were correlated with avermectin production levels. DNase I footprinting and electrophoretic mobility shift assays indicated that SAV576 and SAV577 compete for the same binding regions, and that DNA-binding affinity of SAV576 is much stronger than that of SAV577. GST pull-down assays revealed no direct interaction between the two proteins. Taken together, these findings suggest that SAV577 regulates avermectin production in S. avermitilis by a mechanism similar to that of SAV576, and that the role of SAV576 is dominant over that of SAV577. This is the first report of two adjacent and similar TFR genes that co-regulate antibiotic production in Streptomyces.
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