Person: SARIYAR AKBULUT, BERNA
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SARIYAR AKBULUT
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Publication Open Access Curcumin displays enhanced solubility and antibacterial activities when complexed with the cell penetrating peptide pVEC(2022-06-01) SARIYAR AKBULUT, BERNA; Koleoglu E., Acar T., DERMAN S., SARIYAR AKBULUT B.Curcumin is among phytochemicals with increasing popularity; unfortunately, its therapeutic potential is restricted due to poor water solubility and bioavailability. The current work undertakes the effort to improve the therapeutic potential of curcumin by complexing it with a cell penetrating peptide using copper ions. A mononuclear complex was synthesized from copper(II) acetate and curcumin. Then this complex was conjugated to the cell penetrating peptide, pVEC. The structural characterization of the complexes was achieved using UV-Vis and Fourier transform infrared spectroscopies. Dynamic and electrophoretic light scattering measurements have confirmed the complexation of curcumin with the peptide to form nanoparticles. Both solubility and kinetic stability of curcumin greatly improved upon complex formation with pVEC through copper ions. Then the antibacterial activity of curcumin in the complex was tested. The amount of curcumin in the minimum inhibitory concentration was similar to 30, similar to 8, and similar to 15 fold lower, respectively for Escherichia coli, Bacillus subtilis, and Staphylococcus aureus when complexed with pVEC; however, this improvement was specifically noteworthy for the gram-negative E. coli since the contribution of pVEC in the complex to the observed activity was negligible in this bacterium. With enhanced solubility and stability, metallo curcumin conjugated pVEC complex possesses potential for different therapeutic applications.Publication Metadata only Screening of FDA-Approved Natural Drugs as Anti-Virulence Agents Against Pseudomonas aeruginosa and Neisseria meningitides.(2022-06-30) KULA, CEYDA; ÖZBEK SARICA, PEMRA; SARIYAR AKBULUT, BERNA; Özcan A., Kula C., Avcı F. G., Keskin Özkaya Z. Ö., Özbek Sarıca P., Sarıyar Akbulut B.Publication Open Access Carvacrol enhances the antimicrobial potency of berberine in bacillus subtilis(2022-05-01) SAYAR, NİHAT ALPAGU; SARIYAR AKBULUT, BERNA; Atas B., Aksoy C. S., Avci F. G., SAYAR N. A., Ulgen K., ÖZKIRIMLI ÖLMEZ E., SARIYAR AKBULUT B.The essential oil carvacrol from oregano displays a wide range of biological activities among which is found the inhibition of efflux pumps. Thus, using carvacrol, the current work undertook the effort to potentiate the antimicrobial activity of berberine, a natural product with limited antimicrobial efficacy due to its efflux. Following the selection of concentrations for the combinatorial treatments, guided by checkerboard microtiter plate assay and growth experiments, ethidium bromide accumulation assay was used to find that 25 mu g mL(-1) carvacrol displayed a weak efflux pump inhibitor character in Bacillus subtilis. Scanning electron microscopy images and cellular material leakage assays showed that carvacrol at this concentration neither altered the morphology nor the permeability of the membrane alone but when combined with 75 mu g mL(-1) berberine. Among the efflux pumps of different families found in B. subtilis, except for BmrA and Mdr, the increase in the expressional changes was striking, with Blt displaying similar to 4500-fold increase in expression under the combination treatment. Overall, the findings demonstrated that carvacrol potentiated the effect of berberine; however, not only multiple pumps but also different targets may be responsible for the observed activity.Publication Open Access A review on the mechanistic details of OXA enzymes of ESKAPE pathogens(2023-01-01) SARIYAR AKBULUT, BERNA; ÖZBEK SARICA, PEMRA; Avci F. G., Tastekil I., Jaisi A., ÖZBEK SARICA P., SARIYAR AKBULUT B.The production of beta-lactamases is a prevalent mechanism that poses serious pressure on the control of bacterial resistance. Furthermore, the unavoidable and alarming increase in the transmission of bacteria producing extended-spectrum beta-lactamases complicates treatment alternatives with existing drugs and/or approaches. Class D beta-lactamases, designated as OXA enzymes, are characterized by their activity specifically towards oxacillins. They are widely distributed among the ESKAPE bugs that are associated with antibiotic resistance and life-threatening hospital infections. The inadequacy of current beta-lactamase inhibitors for conventional treatments of \"OXA\" mediated infections confirms the necessity of new approaches. Here, the focus is on the mechanistic details of OXA-10, OXA-23, and OXA-48, commonly found in highly virulent and antibiotic-resistant pathogens Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterobacter spp. to describe their similarities and differences. Furthermore, this review contains a specific emphasis on structural and computational perspectives, which will be valuable to guide efforts in the design/discovery of a common single-molecule drug against ESKAPE pathogens.Publication Open Access Metabolic engineering of Corynebacterium glutamicum for L-tyrosine production from glucose and xylose(2023-02-10) SARIYAR AKBULUT, BERNA; Kurpejović E., Burgardt A., Bastem G. M., Junker N., Wendisch V. F., SARIYAR AKBULUT B.© 2023 Elsevier B.V.Microbial production of aromatic compounds is an attractive and sustainable biotechnological approach. With this motivation, here metabolic engineering of Corynebacterium glutamicum for L-tyrosine (L-Tyr) overproduction was attempted by pushing the carbon flux more towards L-Tyr. Translational start codon exchanges of prephenate dehydratase (pheA), anthranilate synthase (trpE), and phenylalanine aminotransferase (pat) genes revealed that reduced expression of pheA was the major contributor to increased L-Tyr titer while codon exchange in trpE was effective to a lower extent. Overexpression of aroE and qsuC, encoding shikimate dehydrogenase and 3-dehydroquinate dehydratase, respectively, and of dapC (cg1253), which is predicted to encode prephenate aminotransferase, were futile to increase L-Tyr titer. Similarly, deletion of the qsuABD gene cluster had also not enhanced titer. As for increasing precursor supply, deletion of ptsG of glucose uptake and overexpression of inositol permease (iolT2) and glucokinase (glcK) were not effective, but with utilization of xylose, enabled by overexpression of xylose isomerase (xylA) and xylulokinase (xylB), titer improved. Highest L-Tyr titer using the construct was 3.1 g/L on glucose and 3.6 g/L on a 1:3 (w/v) mixture of glucose and xylose. This result displays the potential of the constructed strain to produce L-Tyr from lignocellulosic renewable carbon sources.Publication Metadata only Investigation of the Inhibition of Pseudomonas aeruginosa Type IV Pili Elongation ATPases to Prevent Biofilm Formation.(2022-11-04) KULA, CEYDA; ÖZBEK SARICA, PEMRA; SARIYAR AKBULUT, BERNA; Kula C., Avcı F. G., Keskin Özkaya Z. Ö., Özbek Sarıca P., Sarıyar Akbulut B.Publication Open Access Utilization of orange peel waste for sustainable amino acid production by Corynebacterium glutamicum(2024-01-01) SARIYAR AKBULUT, BERNA; Junker N., SARIYAR AKBULUT B., Wendisch V. F.Oranges are the most processed fruit in the world–it is therefore apparent that the industrial production of orange juice generates large quantities of orange peel as a by-product. Unfortunately, the management of the orange peel waste leads to economic and environmental problems. Meanwhile, the use of sustainable raw materials for the production of bulk chemicals, such as amino acids, is becoming increasingly attractive. To address both issues, this study focused on the use of orange peel waste as a raw material for media preparation for the production of amino acids by engineered Corynebacterium glutamicum. C. glutamicum grew on pure orange peel hydrolysate (OPH) and growth was enhanced by the addition of a nitrogen source and a pH buffer. Inhibitory effects by the combination of high concentrations of OPH, (NH4)2SO4, and MOPS buffer in the wild-type strain (WT), were overcome in the tyrosine-producing engineered C. glutamicum strain AROM3. Genetic modifications that we identified to allow for improved growth rates under these conditions included the deletions of the vanillin dehydrogenase gene vdh, the ʟ-lactate dehydrogenase gene ldhA and the 19 genes comprising cluster cg2663-cg2686. A growth inhibiting compound present in high concentrations in the OPH is 5-(hydroxymethyl)furfural (HMF). We identified vdh as being primarily responsible for the oxidation of HMF to its acid 5-hydroxymethyl-2-furancarboxylic acid (HMFCA), as the formation of HMFCA was reduced by 97% upon deletion of vdh in C. glutamicum WT. In addition, we showed that growth limitations could be overcome by adjusting the media preparation, using a combination of cheap ammonia water and KOH for pH neutralization after acidic hydrolysis. Overall, we developed a sustainable medium based on orange peel waste for the cultivation of C. glutamicum and demonstrated the successful production of the exemplary amino acids ʟ-arginine, ʟ-lysine, ʟ-serine, ʟ-valine and ʟ-tyrosine.