Bacillus subtilis'de basilisin biyosentezinin fonksiyonel rolünün proteom ölçekli analizi.


Tezin Türü: Yüksek Lisans

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

Tezin Onay Tarihi: 2010

Tezin Dili: İngilizce

Öğrenci: Aslı Taşkın Aras

Danışman: GÜLAY ÖZCENGİZ

Özet:

The members of the genus Bacillus produce a wide variety of secondary metabolites with antimetabolic and pharmacological activities. Most of these metabolites are small peptides that have unusual components and chemical bonds and synthesized nonribosomally by multifunctional enzyme complexes called peptide synthetases. Bacilysin, being produced and excreted by certain strains of Bacillus subtilis, is one of the simplest peptide antibiotics known. It is a dipeptide with an N-terminal L-alanine and an unusual amino acid, L-anticapsin, at its C-terminal. Recently, ywfBCDEF operon of B. subtilis 168 was shown to carry bacilysin biosynthesis function, the genes of this operon were renamed as bacABCDE. The first member of bac operon, bacA gene was proved to encode the function of L-alanine –L-anticapsin amino acid ligation. Bacilysin production is regulated at different levels, negatively by GTP via the transcriptional regulator CodY and AbrB while positive regulation occurs by guanosine 5‟-diphosphate 3‟-diphosphate (ppGpp) as well as a quorum-sensing mechanism through the peptide pheromone PhrC. This study aims to identify the functional role of bacilysin biosynthesis in the regulatory cascade operating in B.subtilis by employing proteome-wide analysis of the bacilysin producer B. subtilis PY79 and its bacilysin nonproducer derivative PY79 bacA::lacZ::erm which was recently constructed by our group. The identification of a total of 128 proteins which are differentially expressed in wild type PY79 and bacA inactive strains provided us with the knowledge of interaction of bacilysin biosynthesis with global regulatory pathways and the understanding of the effects of antibiotic production on the expression of the genes with unknown functions in B. subtilis.