Group for Eco-Biotechnology and Drug Development, Univerzitet u Beogradu, Institut za Molekularnu Genetiku i Geneticko Inzenjerstvo, Belgrade, Beograd, Serbia
Dr. Jelena Simić
Group for Eco-Biotechnology and Drug Development, Univerzitet u Beogradu, Institut za Molekularnu Genetiku i Geneticko Inzenjerstvo, Belgrade, Beograd, Serbia
The quest for sustainable biomaterials with excellent biocompatibility and tailorable properties has put polyhydroxyalkanoates (PHAs) into the research spotlight. However, high production costs and the lack of bioactivity limit their market penetration. To address this, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) was combined with a bacterial pigment with strong anticancer activity, prodigiosin (PG), to obtain functionally enhanced PHBV-based biomaterials. The samples were produced in the form of films 115.6–118.8 µm in thickness using the solvent casting method. The effects of PG incorporation on the physical properties (morphology, biopolymer crystallinity and thermal stability) and functionality of the obtained biomaterials were investigated. PG has acted as a nucleating agent, in turn affecting the degree of crystallinity, thermal stability and morphology of the films. All samples with PG had a more organized internal structure and higher melting and degradation temperatures. The calculated degree of crystallinity of the PHBV copolymer was 53%, while the PG1, PG3 and PG3 films had values of 64.0%, 63.9% and 69.2%, respectively. Cytotoxicity studies have shown the excellent anticancer activity of films against HCT116 (colon cancer) cells, thus advancing PHBV biomedical application potential.
Prodigiosins (prodiginines) are a class of bacterial secondary metabolites with remarkable biological activities and color. In this study, optimized production, purification, and characterization of prodigiosin (PG) from easily accessible Serratia marcescens ATCC 27117 strain has been achieved to levels of 14 mg/L of culture within 24 h. Furthermore, environmentally friendly bromination of produced PG was used to afford both novel mono- and dibrominated derivatives of PG. PG and its Br derivatives showed anticancer potential with IC50 values range 0.62–17.00 µg/mL for all tested cancer cell lines and induction of apoptosis but low selectivity against healthy cell lines. All compounds did not affect Caenorhabditiselegans at concentrations up to 50 µg/mL. However, an improved toxicity profile of Br derivatives in comparison to parent PG was observed in vivo using zebrafish (Danio rerio) model system, when 10 µg/mL applied at 6 h post fertilization caused death rate of 100%, 30% and 0% by PG, PG-Br, and PG-Br2, respectively, which is a significant finding for further structural optimizations of bacterial prodigiosins. The drug-likeness of PG and its Br derivatives was examined, and the novel Br derivatives obey the Lipinski’s “rule of five”, with an exemption of being more lipophilic than PG, which still makes them good targets for further structural optimization.
The clinically used antifungal agents, econazole, voriconazole and clotrimazole, were successfully applied in the synthesis of novel silver(i)-azole complexes with significantly improved anti-Candida activity in respect to the parent organic drugs.
The negative environmental and social impacts of food waste accumulation can be mitigated by utilizing bio-refineries’ approach where food waste is revalorized into high-value products, such as prodigiosin (PG), using microbial bioprocesses. The diverse biological activities of PG position it as a promising compound, but its high production cost and promiscuous bioactivity hinder its wide application. Metal ions can modulate the electronic properties of organic molecules, leading to novel mechanisms of action and increased target potency, while metal complex formation can improve the stability, solubility and bioavailability of the parent compound. The objectives of this study were optimizing PG production through bacterial fermentation using food waste, allowing good quantities of the pure natural product for further synthesizing and evaluating copper(II) and zinc(II) complexes with it. Their antimicrobial and anticancer activities were assessed, and their binding affinity toward biologically important molecules, bovine serum albumin (BSA) and DNA was investigated by fluorescence emission spectroscopy and molecular docking. The yield of 83.1 mg/L of pure PG was obtained when processed meat waste at 18 g/L was utilized as the sole fermentation substrate. The obtained complexes CuPG and ZnPG showed high binding affinity towards target site III of BSA, and molecular docking simulations highlighted the affinity of the compounds for DNA minor grooves.
12 January 2018 in Applied Microbiology and Biotechnology