Microbial Phenazines as Potential Enzyme Inhibitors for Metabolic Diseases: Fermentative Production, Kinetic and Docking Studies


Aslan K., Erden Kopar E., Kelle K., Kızıltaş H., Gülçin I.

5th Eurasia Biochemical Approaches & Technologies Congress (EBAT), Antalya, Türkiye, 2 - 05 Kasım 2023, ss.48

  • Yayın Türü: Bildiri / Özet Bildiri
  • Basıldığı Şehir: Antalya
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.48
  • Atatürk Üniversitesi Adresli: Evet

Özet

Phenazines are low molecular weight, heterocyclic compounds that serve as versatile and golden molecules in several industries regarding their broad-spectrum antimicrobial, antitumor, and antiparasitic activity as well as their biological origin, and suitability to a great deal of biotechnological applications 1,2 . The present study aimed to evaluate enzyme inhibition properties of microbial phenazines over enzymes associated with metabolic diseases. For this purpose, phenazine derivatives were produced in chemically defined media by P. chlororaphis subsp. aureofaciens on batch, submerged cultures and purified through solvent extraction followed by adsorption chromatography. Prior to the molecular docking procedure, three different phenazine derivatives were obtained and characterized by spectroscopic techniques including FT-IR, NMR, and UV-Vis. Then the molecular docking procedure was applied to the identified phenazine derivatives using AutoDock Vina 1.1.2. The best docking scores and binding interactions over acetylcholinesterase (AChE), α-glycosidase (AG), carbonic anhydrase I (hCA I) and II (hCA II), butyrylcholinesterase (BChE), and α-amylase (AA) are analyzed by BIOVIA Discovery Studio. As empirical studies, spectrophotometric methods investigated the inhibitory properties of commercially purchased AChE, BChE, AG, AA, and in-house purified (affinity chromatography) hCA I and II enzymes. The kinetic parameters of each enzyme in the presence of the inhibitors were defined and compared with clinically available inhibitors. In conclusion, the potential use of microbial phenazine derivatives in the treatment of Alzheimer’s disease, diabetes, and glaucoma was evaluated. To the best of our knowledge, this is the first study conducted to investigate the anticholinergic, antidiabetic, and antiglaucoma effects of microbial phenazines