Rasemik Propranololün Biyokatalitik Yükseltgenme Tepkimesi için Uygun Mikroorganizma Seçimi

Yıl 2017, Cilt: 5 Sayı: 4, 13 - 25, 22.12.2017

Rahime Songür Ülkü Mehmetoğlu

https://doi.org/10.29109/http-gujsc-gazi-edu-tr.369216

Öz

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

Öz

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.

Anahtar Kelimeler

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

Kaynakça

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