Increasing clavulanic acid production both in wild type and industrial streptomyces clavuligerus strains by amplification of positive regulator claR gene

Download
2012
Mutlu, Alper
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. Among these compounds, clavulanic acid is being used in combination with commonly used β-lactam antibiotics in order to fight against bacterial infections that are resistant to such antibiotics. Among these combinations, Augmentin, composed of amoxicillin and clavulanic acid, is the most widely prescribed drug and has a market value of more than one billion dollars per year. There are two genes that act in regulation of clavulanic acid biosynthesis: ccaR located in cephamycin C gene cluster and claR located in clavulanic acid gene cluster. The goal of this study is to improve clavulanic acid production capacities of both wild type and industrial S. clavuligerus strains by integrating extra copies of claR gene into S.clavuligerus genome and its overexpression via a multicopy plasmid. Although previously has shown to be quite effective on wild type S. clavuligerus strains, claR overexpression in the industrial strain used in this study yielded only 1.4-fold increase in volumetric and 1.7-fold increase in specific CA production by the recombinant strains MA28 and MA16, respectively.

Suggestions

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...
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...
Integration of clavaminate synthase 2 gene into the chromosome of an industrial strain of Streptomyces Clavuligerus for enhanced clavulanic acid production
Vanlı, Güliz; Özcengiz, Gülay; Özkan, Melek; Department of Biotechnology (2010)
Streptomyces clavuligerus is a gram-positive, filamentous bacterium which has a great ability to produce secondary metabolites including isopenicillin N, cephamycin C and a beta-lactamase inhibitor clavulanic acid. Clavulanic acid (CA) which is a bicyclic beta-lactam, inhibits most of class A beta-lactamases by binding irreversibly to the serine hydroxyl group at the active center of beta-lactamases and resulting in the stable acyl-enzyme complexes. Clavaminate synthase (CAS) is one of the best characterize...
Higher alkyl sulfatase activity required by microbial inhabitants to remove anionic surfactants in the contaminated surface waters
İçgen, Bülent; Goksu, Lale; Ulusoy, Huseyin; Yılmaz, Fadime (IWA Publishing, 2017-11-01)
Biodegradation of anionic surfactants, like sodium dodecyl sulfate (SDS) are challenged by some bacteria through the function of the enzyme alkyl sulfatases. Therefore, identifying and characterizing bacteria capable of degrading SDS with high alkyl sulfatase enzyme activity are pivotal. In this study, bacteria isolated from surfactant contaminated river water were screened for their potential to degrade SDS. Primary screening carried out by the conventional enrichment culture technique and assessment of SD...
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...
Citation Formats
A. Mutlu, “Increasing clavulanic acid production both in wild type and industrial streptomyces clavuligerus strains by amplification of positive regulator claR gene,” M.S. - Master of Science, Middle East Technical University, 2012.