ArticleMicrobial cell factories2024
Characterization of a pleiotropic regulator MtrA in Streptomyces avermitilis controlling avermectin production and morphological differentiation.
Article in Microbial cell factories, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed, 10 citations in OpenAlex.
- Regulation of Ansamitocin P-3 Biosynthesis by the Response Regulator CrsB in Actinosynnema pretiosum.Current microbiology · 2026Article
- Heavy metal tolerance in rare actinobacteria from Moroccan mining sites: first report of copper, zinc, and cobalt tolerance and zinc-associated antibacterial activity in Lentzea sp.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Article
- MtrAB activates ectoine production and triggers sporulation in response to osmotic stress inMicrobiology (Reading, England) · 2026Article
- The LuxR family regulator SAV111 enhances avermectin production by binding to aveA1 gene promoter in Streptomyces avermitilis.Archives of microbiology · 2025Article
- AdpA, a Global Regulator of Hundreds of Genes, Including Those for Secondary Metabolism, inAntibiotics (Basel, Switzerland) · 2025Article
- A rapid and efficient strategy for combinatorial repression of multiple genes in Escherichia coli.Microbial cell factories · 2025Article
- Deletions of conserved extracytoplasmic function sigma factors-encoding genes in Streptomyces have a major impact on secondary metabolism.Microbial cell factories · 2024Article
- Potential ofMetabolites · 2024Review
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5 authors at 2 institutions in 1 country.
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Abstract
backgroundThe macrolide antibiotic avermectin, a natural product derived from Streptomyces avermitilis, finds extensive applications in agriculture, animal husbandry and medicine. The mtrA (sav_5063) gene functions as a transcriptional regulator belonging to the OmpR family. As a pleiotropic regulator, mtrA not only influences the growth, development, and morphological differentiation of strains but also modulates genes associated with primary metabolism. However, the regulatory role of MtrA in avermectin biosynthesis remains to be elucidated.
resultsIn this study, we demonstrated that MtrA, a novel OmpR-family transcriptional regulator in S. avermitilis, exerts global regulator effects by negatively regulating avermectin biosynthesis and cell growth while positively controlling morphological differentiation. The deletion of the mtrA gene resulted in an increase in avermectin production, accompanied by a reduction in biomass and a delay in the formation of aerial hyphae and spores. The Electrophoretic Mobility Shift Assay (EMSA) revealed that MtrA exhibited binding affinity towards the upstream region of aveR, the intergenic region between aveA1 and aveA2 genes, as well as the upstream region of aveBVIII in vitro. These findings suggest that MtrA exerts a negative regulatory effect on avermectin biosynthesis by modulating the expression of avermectin biosynthesis cluster genes. Transcriptome sequencing and fluorescence quantitative PCR analysis showed that mtrA deletion increased the transcript levels of the cluster genes aveR, aveA1, aveA2, aveC, aveE, aveA4 and orf-1, which explains the observed increase in avermectin production in the knockout strain. Furthermore, our findings demonstrate that MtrA positively regulates the cell division and differentiation genes bldM and ssgC, while exerting a negative regulatory effect on bldD, thereby modulating the primary metabolic processes associated with cell division, differentiation and growth in S. avermitilis, consequently impacting avermectin biosynthesis.
conclusionsIn this study, we investigated the negative regulatory effect of the global regulator MtrA on avermectin biosynthesis and its effects on morphological differentiation and cell growth, and elucidated its transcriptional regulatory mechanism. Our findings indicate that MtrA plays crucial roles not only in the biosynthesis of avermectin but also in coordinating intricate physiological processes in S. avermitilis. These findings provide insights into the synthesis of avermectin and shed light on the primary and secondary metabolism of S. avermitilis mediated by OmpR-family regulators.
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