ArticleMicrobial cell factories2015
Identification of a cluster-situated activator of oxytetracycline biosynthesis and manipulation of its expression for improved oxytetracycline production in Streptomyces rimosus.
Article in Microbial cell factories, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 64 citations in OpenAlex.
- The Oxytetracycline ProducerInternational journal of molecular sciences · 2026Article
- Development of a versatile chassis for the efficient production of diverse type II polyketides.Nature communications · 2025Article
- Actinobacteria: Smart Micro-Factories for The Health Sector.Recent patents on biotechnology · 2025Review
- Coordinated regulation of two LacI family regulators, GvmR and GvmR2, on guvermectin production inSynthetic and systems biotechnology · 2025Article
- Engineering Streptomyces sp. CPCC 204095 for the targeted high-level production of isatropolone A by elucidating its pathway-specific regulatory mechanism.Microbial cell factories · 2024Article
- Transcriptional regulators of secondary metabolite biosynthesis in Streptomyces.World journal of microbiology & biotechnology · 2024Review
- The roles of SARP family regulators involved in secondary metabolism inFrontiers in microbiology · 2024Review
- Systems biology of industrial oxytetracycline production in Streptomyces rimosus: the secrets of a mutagenized hyperproducer.Microbial cell factories · 2023Article
- Metabolic engineering ofEngineering microbiology · 2022Review
- Discovery, Yield Improvement, and Application in Marine Coatings of Potent Antifouling Compounds Albofungins Targeting Multiple Fouling Organisms.Frontiers in microbiology · 2022Article
- Heat Shock Repressor HspR Directly Controls Avermectin Production, Morphological Development, and HApplied and environmental microbiology · 2021Article
- Biodiversity of Secondary Metabolites Compounds Isolated from Phylum Actinobacteria and Its Therapeutic Applications.Molecules (Basel, Switzerland) · 2021Review
- Mannose- and Mannobiose-Specific Responses of the Insect-Associated Cellulolytic BacteriumApplied and environmental microbiology · 2021Article
- Development of aJournal of Zhejiang University. Science. B · 2021Article
- Heterologous expression of the atypical tetracycline chelocardin reveals the full set of genes required for its biosynthesis.Microbial cell factories · 2020Article
- Metabolic engineering of a methyltransferase for production of drug precursors demecycline and demeclocycline inSynthetic and systems biotechnology · 2020Article
- Biosynthesis of aromatic polyketides in microorganisms using type II polyketide synthases.Microbial cell factories · 2020Review
- The regulatory cascades of antibiotic production in Streptomyces.World journal of microbiology & biotechnology · 2020Review
- Harnessing the intracellular triacylglycerols for titer improvement of polyketides in Streptomyces.Nature biotechnology · 2020Article
- Corrigendum: The Application of Regulatory Cascades inFrontiers in microbiology · 2020Article
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOxytetracycline (OTC) is a broad-spectrum antibiotic commercially produced by Streptomyces rimosus. Despite its importance, little is known about the regulation of OTC biosynthesis, which hampered any effort to improve OTC production via engineering regulatory genes.
resultsA gene encoding a Streptomyces antibiotic regulatory protein (SARP) was discovered immediately adjacent to the otrB gene of oxy cluster in S. rimosus and designated otcR. Deletion and complementation of otcR abolished or restored OTC production, respectively, indicating that otcR encodes an essential activator of OTC biosynthesis. Then, the predicted consensus SARP-binding sequences were extracted from the promoter regions of oxy cluster. Transcriptional analysis in a heterologous GFP reporter system demonstrated that OtcR directly activated the transcription of five oxy promoters in E. coli, further mutational analysis of a SARP-binding sequence of oxyI promoter proved that OtcR directly interacted with the consensus repeats. Therefore, otcR was chosen as an engineering target, OTC production was significantly increased by overexpression of otcR as tandem copies each under the control of strong SF14 promoter.
conclusionsA SARP activator, OtcR, was identified in oxy cluster of S. rimosus; it was shown to directly activate five promoters from oxy cluster. Overexpression of otcR at an appropriate level dramatically increased OTC production by 6.49 times compared to the parental strain, thus demonstrating the great potential of manipulating OtcR to improve the yield of OTC production.
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