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

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Tezin Türü: Yüksek Lisans

Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Fen Edebiyat Fakültesi, Biyolojik Bilimler Bölümü, Türkiye

Tezin Onay Tarihi: 2012

Öğrenci: ALPER MUTLU

Danışman: GÜLAY ÖZCENGİZ

Özet:

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.