ArticleJournal of bacteriology2008
Identification and utility of FdmR1 as a Streptomyces antibiotic regulatory protein activator for fredericamycin production in Streptomyces griseus ATCC 49344 and heterologous hosts.
Article in Journal of bacteriology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 92 citations in OpenAlex.
- Unlocking the Bioactive Potential of Streptomyces: A Multidisciplinary Approach to Strain Improvement.MicrobiologyOpen · 2026Review
- Exploring marine-derived compounds as potential anti-cancer agents: Mechanisms and therapeutic implications.Cancer pathogenesis and therapy · 2026Review
- Review
- Enhancing Secondary Metabolite Production in Actinobacteria Through Over-Expression of a Medium-Sized SARP Regulator.International journal of molecular sciences · 2025Article
- The LysR family transcriptional regulator ORF-L16 regulates spinosad biosynthesis inSynthetic and systems biotechnology · 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
- Focus and Insights into the Synthetic Biology-Mediated Chassis of Economically Important Fungi for the Production of High-Value Metabolites.Microorganisms · 2023Review
- Regulated Expression of an Environmental DNA-Derived Type II Polyketide Gene Cluster in Streptomyces Hosts Identified a New Tetracenomycin Derivative TCM Y.Current microbiology · 2022Article
- MilR3, a unique SARP family pleiotropic regulator in Streptomyces bingchenggensis.Archives of microbiology · 2022Article
- Genome-scale analysis of genetic regulatory elements in Streptomyces avermitilis MA-4680 using transcript boundary information.BMC genomics · 2022Article
- High-Throughput Transcriptional Characterization of Regulatory Sequences from Bacterial Biosynthetic Gene Clusters.ACS synthetic biology · 2021Article
- Review
- System-level understanding of gene expression and regulation for engineering secondary metabolite production in Streptomyces.Journal of industrial microbiology & biotechnology · 2020Review
- Disclosing the Potential of the SARP-Type Regulator PapR2 for the Activation of Antibiotic Gene Clusters in Streptomycetes.Frontiers in microbiology · 2020Article
- Biosynthesis of Polyketides inMicroorganisms · 2019Review
- Leveraging synthetic biology for producing bioactive polyketides and non-ribosomal peptides in bacterial heterologous hosts.MedChemComm · 2019Review
- Challenges and opportunities for natural product discovery, production, and engineering in native producers versus heterologous hosts.Journal of industrial microbiology & biotechnology · 2019Review
- High-Yield Production of Herbicidal Thaxtomins and Thaxtomin Analogs in a Nonpathogenic Streptomyces Strain.Applied and environmental microbiology · 2018Article
- New Kid on the Block: LmbU Expands the Repertoire of Specialized Metabolic Regulators in Streptomyces.Journal of bacteriology · 2018Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The fredericamycin (FDM) A biosynthetic gene cluster, cloned previously from Streptomyces griseus ATCC 49344, contains three putative regulatory genes, fdmR, fdmR1, and fdmR2. Their deduced gene products show high similarity to members of the Streptomyces antibiotic regulatory protein (SARP) family (FdmR1) or to MarR-like regulators (FdmR and FdmR2). Here we provide experimental data supporting FdmR1 as a SARP-type activator. Inactivation of fdmR1 abolished FDM biosynthesis, and FDM production could be restored to the fdmR1::aac(3)IV mutant by expressing fdmR1 in trans. Reverse transcription-PCR transcriptional analyses revealed that up to 26 of the 28 genes within the fdm gene cluster, with the exception of fdmR and fdmT2, were under the positive control of FdmR1, directly or indirectly. Overexpression of fdmR1 in S. griseus improved the FDM titer 5.6-fold (to about 1.36 g/liter) relative to that of wild-type S. griseus. Cloning of the complete fdm cluster into an integrative plasmid and subsequent expression in heterologous hosts revealed that considerable amounts of FDMs could be produced in Streptomyces albus but not in Streptomyces lividans. However, the S. lividans host could be engineered to produce FDMs via constitutive expression of fdmR1; FDM production in S. lividans could be enhanced further by overexpressing fdmC, encoding a putative ketoreductase, concomitantly with fdmR1. Taken together, these studies demonstrate the viability of engineering FDM biosynthesis and improving FDM titers in both the native producer S. griseus and heterologous hosts, such as S. albus and S. lividans. The approach taken capitalizes on FdmR1, a key activator of the FDM biosynthetic machinery.
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Registered trials
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.