Structure optimisation of biopigment prodigiosin from Serratia marcescens ATCC 27117 and antimicrobial and anticancer properties of novel halogenated derivativesJelena Lazić
, 2022, doktorska disertacija
Opis: Prodigiosins (PGs) are a class of bacterial secondary metabolites with remarkable biological activities and colour. In this study, optimised fermentative production of prodigiosin (PG) using waste processed meat as a substrate has been achieved to levels of 83.1 ± 3.0 mg/L from a commercially available Serratia marcescens ATCC 27117 strain within 12 h. Methods were established for the reliable PG extraction from both the bacterial cell pellet and the culture supernatant, while gravitation column chromatography was used to obtain pure bacterial PG.
The structure of the isolated PG was optimised by environmentally acceptable oxidative bromination reactions, obtaining mono- and dibrominated derivatives (PG-Br and PG-Br2). Chemical structures were confirmed by structural characterisation using nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS), showing that PG-Br is a mixture of two monobrominated isomers in approximately equal ratios, while PG-Br2 was afforded as a pure derivative.
PG and its brominated derivatives (Br-derivatives) showed anticancer potential with half-maximal inhibitory concentration (IC50) values ranging from 0.62 to 17.00 μg/mL on four tested cancer cell lines (A549 lung, A375 skin, MDA-MB-231 breast, HCT116 colon) and an induction of early apoptosis, but low selectivity against healthy cell lines (MRC-5 lung fibroblasts and HaCaT skin keratinocytes). All three PG, PG-Br and PG-Br2 compounds did not affect roundworms (Caenorhabditis elegans) at concentrations up to 50 μg/mL. However, an improved toxicity profile of Br-derivatives in comparison to the parent PG was observed in vivo using zebrafish (Danio rerio) model system, when 10 μg/mL applied at 6 h post fertilisation caused death rate of 100, 30 and 0% by PG, PG-Br and PG-Br2, respectively, which is a significant finding for further structural optimisations of bacterial PGs.
Najdeno v: ključnih besedah
Ključne besede: prodigiosin, Serratia marcescens, meat waste, halogenation, novel derivatives, anticancer activity, apoptosis, zebrafish embryotoxicity
Objavljeno: 21.10.2022; Ogledov: 462; Prenosov: 20
Polno besedilo (3,39 MB)