Rasemik Propranololün Biyokatalitik Yükseltgenme Tepkimesi için Uygun Mikroorganizma Seçimi

Propranolol; farmasötik açıdan önem taşıyan, özellikle kardiyovasküler hastalıkların tedavisinde yaygın olarak kullanılan β-blokerlardan biridir. Bu çalışmada, propranololün enantiyomerik saflıkta üretiminin, rasemik propranololün ardışık yükseltgenme-indirgenme tepkimelerini içeren biyokatalitik derasemizasyonu prosesiyle gerçekleştirilmesi amaçlanmaktadır. Bu kapsamda öncelikle rasemik propranololün yükseltgenme tepkimesinde kullanılacak uygun mikroorganizma araştırılmıştır. Propranololün yükseltgenmesi için alkol dehidrojenaz (ADH) enzimi ve bu enzimin aktivite gösterebilmesi amacıyla ihtiyaç duyulan kofaktörün rejenerasyonu için ise NADH oksidaz enzimi gereklidir. Bu doğrultuda, tepkimede enzim kaynağı olarak kullanılacak mikroorganizmanın seçimi için farklı mikroorganizmalardaki (Lactobacillus kefir NRRL B-1839, Rhodotorula glutunis DSM 70398, Rhizopus oryzae CBS 111718, Rhizopus arhizus) ADH ve NADH oksidaz aktiviteleri ölçülmüştür. Kullanılan mikroorganizmalar arasında en yüksek ADH ve NADH oksidaz aktivitesi L. kefir’de bulunmuştur.

Anahtar Kelimeler:

Propranolol, β-bloker, yükseltgenme, ADH, NADH oksidaz

Selection of Suitable Microorganism for Biocatalytic Oxidation Reaction of Racemic Propranolol

Propranolol is one of the β-blockers which are pharmaceutically important, especially used for treatment of cardiovasculer disease. In this study, the production of enantiomerically pure propranolol was aimed via biocatalytic deracemization including tandem oxidation-reduction reactions of racemic propranolol. Within this content, firstly suitable microorganism for the oxidation of racemic propranolol was investigated. Alcohol dehydrogenase (ADH) enzyme for oxidation of propranolol and NADH oxidase enzyme for cofactor regeneration were necessary for the oxidation reactions. For this reason, ADH and NADH oxidase enzymes activities of different microorganisms were measured to select the microorganism for using as enzyme source. These microorganisms are Lactobacillus kefir NRRL B-1839, Rhodotorula glutunis DSM 70398, Rhizopus oryzae CBS 111718, Rhizopus arhizus. The highest ADH and NADH oxidase activities were obtained for L. kefir.

Keywords:

Propranolol, β-blocker, oxidation, ADH, NADH oxidase,

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