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Streptomyces clavuligerus NRRL 3585 is a native producer of clavulanic acid (CA), a clinically used β-lactamase inhibitor, and is widely used as an industrial strain for the production of antibiotics. Selective random mutagenesis has successfully generated the improved CA-producing S. clavuligerus mutant strains as well as the strain with the loss of CA biosynthesis. To understand the molecular mechanisms associated with the improved CA-production potential, genome-scale RNA-sequencing-based transcriptional data were obtained for the wild-type S. clavuligerus strain and its three mutant strains. Total RNA samples for each strain were collected across four different growth stages, and all 32 sequencing data points exhibited an average Phred score of 36. The high-quality genome-scale transcriptional profile of S. clavuligerus strains with varied CA biosynthetic potential provides valuable insights and new opportunities for discovering efficient metabolic engineering strategies for the development of improved industrial strains.
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http://dx.doi.org/10.1038/s41597-023-02727-6 | DOI Listing |
mSphere
August 2025
Department of Biology, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
Unlabelled: β-Lactam antibiotics and β-lactamase inhibitor combinations are essential for combating antimicrobial resistance, with many β-lactams, including clavulanic acid (CA), themselves being products of specialized metabolic pathways in bacteria. CA is a potent β-lactamase inhibitor, and in known producers such as , it is co-produced with the β-lactam antibiotic cephamycin C, and their biosynthetic gene clusters (BGCs) are always located adjacent on the chromosome. However, CA-like BGCs have also been identified in other bacteria, often without an accompanying cephamycin C BGC.
View Article and Find Full Text PDFNucleic Acids Res
June 2025
Department of Computational Biology, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University in Poznań, Poznań 61-614, Poland.
In recent years, Term-seq became a standard experimental approach for high-throughput identification of 3' ends of bacterial transcripts. It was widely adopted to study transcription termination events and 3' maturation of bacterial RNAs. Despite widespread utilization, a universal bioinformatics toolkit for comprehensive analysis of Term-seq sequencing data is still lacking.
View Article and Find Full Text PDFOrg Lett
June 2025
Latvian Institute of Organic Synthesis, Aizkraukles Street 21, LV-1006 Riga, Latvia.
Biarylitides are a new class of ribosomally synthesized and post-translationally modified peptides (RiPPs) with the unique feature of biaryl C-C, C-N, or C-O cross-links installed by P450 biarylitide synthases (P450s). Here, we manually identified 435 homologous P450s linked to putative biarylitide precursor peptides, which is the most extensive list of biarylitide precursor peptide so far reported. Through functional studies in , the newly identified enzyme ShyB from F613-1 was found to catalyze formation of a cross-link between His-C2 and Tyr-O4 on the precursor peptide ShyA.
View Article and Find Full Text PDFMetabolites
May 2025
Grupo de Investigación en Simulación, Diseño, Control y Optimización de Procesos (SIDCOP), Departamento de Ingeniería Química, Universidad de Antioquia, Medellín 050010, Colombia.
Clavulanic acid (CA) is produced by cell suspension cultures of ATCC 27064, and is widely used as a beta-lactamase inhibitor to combat antibiotic resistance. CA titers are moderate due to bioprocess complexity, prompting ongoing efforts to overcome these limitations. In this study, we aimed to evaluate the effect of live and inactivated FZB42 cells on CA production in , and to explore the transcriptional response underlying this interaction using RNA-seq technology.
View Article and Find Full Text PDFEnzyme Microb Technol
September 2025
Department of Biological Sciences and Biotechnology, Institute of Chemical Technology, Matunga, Mumbai, Maharashtra 400019, India. Electronic address:
1,8-Cineole, a monoterpene with diverse industrial and pharmaceutical applications, has garnered significant interest due to its unique properties. This study aims to achieve sustainable production of 1,8-cineole from Yarrowia lipolytica through metabolic and media engineering strategies. The heterologous 1,8-cineole synthase from Streptomyces clavuligerus was integrated through CRISPR-Cas9, along with overexpression of key genes in the mevalonate pathway and a double mutation in the Erg20p to enhance flux towards geranyl pyrophosphate.
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