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

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