Radecka, IzabelaParati, Mattia2025-08-282025-08-282025Parati, M. (2025) The role of γ-polyglutamic acid in a circular economy: cost-effective production and wide-ranging applications of a bio-derived, biodegradable, and nonimmunogenic biomaterial. University of Wolverhampton. https://wlv.openrepository.com/handle/2436/626059https://wlv.openrepository.com/handle/2436/626059This thesis is submitted for the degree of Doctor of Philosophy.Microbial products have long been investigated for their potential as backbones of biodegradable constructs. Poly-γ-glutamic acid (γ-PGA) is an anionic pseudo polypeptide produced by several microorganisms, especially members of the Bacillus species. γ-PGA is synthesised through several enzymes and complexes which racemise and polymerise L- glutamic acid or D- glutamic acid. This non-toxic microbial product can have variable viscosity, is water soluble, biodegradable, and non-immunogenic. The scope of this work was to investigate the effect of substrate components on the chemical and physical characteristics of γ-PGA (Chapter 3). To increase cost-effectiveness and adoption of γ-PGA, further investigation into the effect of different complex media on the yields and composition of resulting material was evaluated (Chapter 3). Subsequently, the potential of γ-PGA from standard cultivation media and complex media as a substitute for hyaluronic acid in cosmetics was evaluated (Chapter 4). UV protective effects of γ-PGA and seaweed rich, crude γ-PGA extracts was assessed and quantified (Chapter 4) and its potential interaction with skin keratinocytes was quantified. γ-PGA ability to interact with ions was assessed in the context of dental demineralisation and prevention thereof (Chapter 5). Potential protein-protein interaction of γ-PGA with monomeric and aggregate forms of alpha synuclein, was assessed in the context of Parkinson disease pathology (Chapter 6). Ultimately the inflammatory response of γ-PGA and γ-PGA-based composites (whey protein isolate- γ-PGA) were also evaluated (Chapter 7). This investigation found the ability of specific ions (Mn2+ and NaCl) to affect the yields and properties of γ-PGA in both standard (GS/Medium E) and complex media (seaweed based). γ-PGA synthesised from complex media could be purified through membrane-based separation technologies although further optimisation is required to selectively removed undesirable impurities. Although commercial γ-PGA was not found to have any UV protection capacity, standard media γ-PGA had some UV protective capacity with complex media derived γ-PGA having the highest protection. No γ-PGA was found to have any detrimental effect on tested HaCaT keratinocyte cells. Both standard and complex media derived γ-PGA did suggest ability to physically bind to components of hydroxyapatite, component of the tooth enamel. Further, our data suggests that γ-PGA is able to co-localise with Parkinson disease specific alpha synuclein aggregates and disrupt further addition of monomeric components onto pre-formed fibrils. In addition, both γ-PGA and pre-formed fibrils of alpha synuclein were shown to be internalised within astrocyte cytoplasm when introduced in the media. Ultimately, γ-PGA addition has shown to significantly decrease inflammatory status of osteoblasts and astrocytes in vitro. This work explores innovative applications of γ-PGA, synthesised from complex media. Fundamental properties of γ-PGA that can be obtained in standard (GS media, Medium E and similar) and complex media have been evaluated for comprehensive understanding on property-application relationship and its potential scale up applications. This work elaborates on how γ-PGA could be the key to the next generation of microbial derived bioproducts.application/pdfenbiotechnologybiopolymermicrobial biotechnologybiomaterialscircular bioprocessesThesis or dissertation