Akademik Veri Yönetim Sistemi
Tezin Türü: Doktora
Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Fen Edebiyat Fakültesi, Biyolojik Bilimler Bölümü, Türkiye
Tezin Onay Tarihi: 2016
Tezin Dili: İngilizce
Öğrenci: Eser Ünsaldı
Danışman: GÜLAY ÖZCENGİZ
Özet:In this study, two cephamycin C (CC) overproducers, Streptomyces clavuligerus AK39 and TB3585 strains, and a clavulanic acid (CA) overproducer S. clavuligerus DEPA were subjected to proteomic analysis to elucidate their differential protein expression profiles when compared to that of the standard strain S. clavuligerus NRRL 3585. Two proteomics approaches were employed: 2DE technique coupled with MALDI-TOF/MS and LC-MS/MS. By using two techniques, a total of 40 proteins were identified as upregulated while 70 proteins were downregulated in AK39. For TB3585 strain, a total of 44 proteins were overrepresented while 50 proteins were underrepresented. For both AK39 and TB3585, “Hypothetical/Unknown Proteins” category harbored higher numbers of upregulated proteins which was followed by “Secondary Metabolism”. Both CC overproducers specifically overexpressed enzymes related with CC biosynthesis and underexpressed proteins involved in the biosynthesis of diverse secondary metabolites like clavams and polyketides. As for the DEPA strain, a total of 80 proteins were upregulated, and 174 proteins were downregulated. Upregulated protein categories in DEPA were ranked as “Hypothetical/Unknown”, “Others/General Function”, “DNA Replication, Recombination, Repair, Transcription” and “Secondary Metabolism”, respectively. Three CA biosynthetic enzymes as well as CcaR were overrepresented whereas enzymes of two other secondary metabolites were underrepresented along with two important global regulators. A decrease in amino acid metabolism, particularly in methionine biosynthesis, appeared as one of the prominent mechanisms of success of DEPA strain as a prolific producer of CA. Results described herein provide useful information for further improvement of CC and CA production in S. clavuligerus with rational approaches.