Comparative Transcriptome Analyses of a Standard Strain and Clavulanic Acid Overproducing Industrial Strain of S. clavuligerus

Çelik, Gözde
Streptomyces clavuligerus is the producer of the medically important β-lactam antibiotics, including cephamycin C (CC) and potent β-lactamase inhibitor clavulanic acid (CA). In this study, comparative transcriptome analysis between an industrial stain, namely DEPA (CA overproducer strain which was developed by several rounds of classical random mutagenesis), and a reference strain NRLL3585 was performed by using the genome-wide RNA-seq technique. Our aim was to understand and improve the knowledge about the complex mechanisms of clavulanic acid overproduction and find out novel targets for use of gene technologies (rational approach) for industrial strain development. According to RNA-seq analysis, structural genes of CA biosynthesis, arginine biosynthesis, G3P synthesis, clavam biosynthesis, and other additional genes/gene clusters that have some role in CA production as well as several regulatory genes like AdpA, TetR/AcrR, and CarD were found to be meaningfully up- or -downregulated. Transcriptomic findings as were also integrated to those of a recent comparative proteome analysis via nanoLC/MS MS obtained in our laboratory. Positive correlation between integrative transcriptomic and proteomic analysis provided more precise insights into the mechanisms of CA overproduction in Streptomyces clavuligerus DEPA.


Quantitative expression analysis of the genes potentially involved in clavulanic acid overproduction in streptomyces clavuligerus
Aktaş, Caner; Özcengiz, Gülay; Department of Molecular Biology and Genetics (2018)
Streptomyces clavuligerus is the producer of the medically important β-lactam antibiotics, including cephamycin C (CC) and the potent β-lactamase inhibitor clavulanic acid. (CA). We have already undertaken an extensive comparative proteomic analysis by using both 2-DE-MALDI-MS and GeLC-MS approaches between an industrial CA overproducer, namely DEPA and the reference strain NRRL3585. In this context, we documented several differentially expressed (over- and under-represented) proteins accounting for high CA...
An integrative-omics analysis of an industrial clavulanic acid-overproducing Streptomyces clavuligerus
KURT KIZILDOĞAN, ASLIHAN; Celik, Gozde; unsaldi, Eser; ÖZCAN, SERVET; AYAZ GÜNER, ŞERİFE; Özcengiz, Gülay (2022-09-01)
Clavulanic acid (CA) is a clinically important secondary metabolite used to treat infectious diseases. We aimed to decipher complex regulatory mechanisms acting in CA biosynthesis by analyzing transcriptome- and proteome-wide alterations in an industrial CA overproducer Streptomyces clavuligerus strain, namely DEPA and its wild-type counterpart NRRL3585. A total of 924 differentially expressed genes (DEGs) and 271 differentially produced proteins (DPPs) were obtained by RNA-seq and nanoLC-MS/MS analyses, re...
The regulatory effect of CcaR activator on the cephamycin C gene cluster of streptomyces clavuligerus
Kurt, Aslıhan; Özcengiz, Gülay; Department of Biology (2011)
Streptomyces clavuligerus produces industrially important secondary metabolites such as cephamycin C (a β-lactam antibiotic) and clavulanic acid (a potent β-lactamase inhibitor). Cephamycin C is active against penicillin-resistant bacteria due to presence of methoxyl group in C-7 position of cephalosporin nucleus. Clavulanic acid is prescribed in combination with β-lactams for treatment of various bacterial infections. Cephamycin C and clavulanic acid gene clusters form β-lactam supercluster in S. clavulige...
Genetic engineering of glycolytic pathway by disrupting glyceraldehyde-3-phosphate dehydrogenase gene in an industrial strain of streptomyces clavuligerus
Sertdemir, İbrahim; Özcengiz, Gülay; Department of Biology (2013)
Streptomyces clavuligerus is a gram-positive, filamentous bacterium which produces several important secondary metabolites, including isopenicillin N, cephamycin C and the β-lactamase inhibitor, clavulanic acid (CA). CA is being used in combination with commonly used β-lactam antibiotics in order to fight against bacterial infections that are resistant to such antibiotics. Glyceraldehyde-3-phosphate (GAP) which is an intermediate product of glycolytic pathway is also used in CA biosynthesis as a crucial sub...
Molecular cloning, characterization, and homologous expression of an endochitinase gene from Bacillus thuringiensis serovar morrisoni
Okay, Sezer; Özcengiz, Gülay (2011-01-01)
The endochitinase gene (chi3023) of Bacillus thuringiensis (Bt) serovar morrisoni strain 3023 was amplified via polymerase chain reaction (PCR) and cloned in Escherichia coli. The ORF of chi3023 (GenBank Accession Number: DQ993175) consists of 2031 nucleotides encoding a 676-residue protein with a calculated molecular mass of 74.5 kDa and a pI value of 6.0. The amino acid sequence of Chi3023 was compared with previously sequenced Bt chitinases and the phylogenetic relationships among them were determined. T...
Citation Formats
G. Çelik, “Comparative Transcriptome Analyses of a Standard Strain and Clavulanic Acid Overproducing Industrial Strain of S. clavuligerus,” M.S. - Master of Science, Middle East Technical University, 2021.