ArticleJournal of industrial microbiology & biotechnology2015
Characterization of negative regulatory genes for the biosynthesis of rapamycin in Streptomyces rapamycinicus and its application for improved production.
Article in Journal of industrial microbiology & biotechnology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 46 citations in OpenAlex.
- Synthetic Biology of Plants and Microbes for Agriculture, Environment, and Future Applications.Chemical reviews · 2026Review
- Advances in natural product discovery: strategies, technologies, and insights.Natural products and bioprospecting · 2026Review
- Rapamycin Plays a Pivotal Role in the Potent Antifungal Activity Exhibited AgainstMicroorganisms · 2025Article
- Transcriptional regulators of secondary metabolite biosynthesis in Streptomyces.World journal of microbiology & biotechnology · 2024Review
- Effect of Precursors and Their Regulators on the Biosynthesis of Antibiotics inMolecules (Basel, Switzerland) · 2024Review
- Manipulation and epigenetic control of silent biosynthetic pathways in actinobacteria.World journal of microbiology & biotechnology · 2024Review
- Identification and Characterization of a New Regulator, TagR, for Environmental Stress Resistance Based on the DNA Methylome of Streptomyces roseosporus.Microbiology spectrum · 2023Article
- Crossregulation of rapamycin and elaiophylin biosynthesis by RapH in Streptomyces rapamycinicus.Applied microbiology and biotechnology · 2022Article
- Review
- High-dose rapamycin exerts a temporary impact on T. reesei RUT-C30 through gene trFKBP12.Biotechnology for biofuels · 2021Article
- The Application of Regulatory Cascades inFrontiers in microbiology · 2020Review
- Regulation of Bottromycin Biosynthesis Involves an Internal Transcriptional Start Site and a Cluster-Situated Modulator.Frontiers in microbiology · 2020Article
- Recent advances in natural products exploitation inEngineering in life sciences · 2019Review
- A Review of the Microbial Production of Bioactive Natural Products and Biologics.Frontiers in microbiology · 2019Review
- Regulatory genes and their roles for improvement of antibiotic biosynthesis in Streptomyces.3 Biotech · 2017Review
- Insights into the metabolic mechanism of rapamycin overproduction in the shikimate-resistant Streptomyces hygroscopicus strain UV-II using comparative metabolomics.World journal of microbiology & biotechnology · 2017Article
- An overview of rapamycin: from discovery to future perspectives.Journal of industrial microbiology & biotechnology · 2017Review
- Advancement in bioprocess technology: parallels between microbial natural products and cell culture biologics.Journal of industrial microbiology & biotechnology · 2017Review
- An Efficient Method To Generate Gene Deletion Mutants of the Rapamycin-Producing Bacterium Streptomyces iranensis HM 35.Applied and environmental microbiology · 2016Article
- Genetic manipulation of secondary metabolite biosynthesis for improved production in Streptomyces and other actinomycetes.Journal of industrial microbiology & biotechnology · 2016Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sequence analysis of the rapamycin biosynthetic gene cluster in Streptomyces rapamycinicus ATCC 29253 identified several putative regulatory genes. The deduced product of rapY, rapR, and rapS showed high sequence similarity to the TetR family transcription regulators, response regulators and histidine kinases of two-component systems, respectively. Overexpression of each of the three genes resulted in a significant reduction in rapamycin production, while in-frame deletion of rapS and rapY from the S. rapamycinicus chromosome improved the levels of rapamycin production by approximately 4.6-fold (33.9 mg l(-1)) and 3.7-fold (26.7 mg l(-1)), respectively, compared to that of the wild-type strain. Gene expression analysis by semi-quantitative reverse transcription-PCR (RT-PCR) in the wild-type and mutant strains indicated that most of the rapamycin biosynthetic genes are regulated negatively by rapS (probably through its partner response regulator RapR) and rapY. Interestingly, RapS negatively regulates the expression of the rapY gene, and in turn, rapX encoding an ABC-transporter is negatively controlled by RapY. Finally, overexpression of rapX in the rapS deletion mutant resulted in a 6.7-fold (49 mg l(-1)) increase in rapamycin production compared to that of wild-type strain. These results demonstrate the role of RapS/R and RapY as negative regulators of rapamycin biosynthesis and provide valuable information to both understand the complex regulatory mechanism in S. rapamycinicus and exploit the regulatory genes to increase the level of rapamycin production in industrial strains.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.