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

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Gözde Çelik - Thesis.pdf

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2021-9

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Çelik, Gözde

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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.

Subject Keywords

Streptomyces clavuligerus, Clavulanic acid overproduction, Genome-wide RNA seq analysis, Proteome, Integrated -omic analysis

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https://hdl.handle.net/11511/93258

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Graduate School of Natural and Applied Sciences, Thesis

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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.