Chemical characterisation and determination of sensory attributes of hydrolysates produced by enzymatic hydrolysis of whey proteins following a novel integrative process

The overall aim of this work was to characterize the major angiotensin converting enzyme (ACE) inhibitory peptides produced by enzymatic hydrolysis of whey proteins, through the application of a novel integrative process. This process consisted of the combination of adsorption and microfiltration within a stirred cell unit for the selective immobilization of β-lactoglobulin and casein derived peptides (CDP) from whey. The adsorbed proteins were hydrolyzed in-situ which resulted in the separation of peptide products from the substrate and fractionation of peptides. Two different hydrolysates were produced: (i) from CDP (IC50 =287μg/mL) and (ii) from β-lactoglobulin (IC50=128μg/mL). IC50 is the concentration of inhibitor needed to inhibit ACE by half. The well known antihypertensive peptide IPP and several novel peptides that have structural similarities with reported ACE inhibitory peptides were identified and characterized in both hydrolysates. Furthermore, the hydrolysates were assessed for bitterness. No significant difference was found between the control (milk with no hydrolysate) and hydrolysate samples at different concentrations (at, below and above the IC50)

Doctor of Philosophy

dissertationNatural products are structurally complex molecules and often exhibit intriguing biological activities. They are, however, notoriously difficult to supply, whether by chemical synthesis or isolation from a living organism. Recently, reconstitution of natural product biosynthetic pathways in a heterologous host has proved a successful strategy for producing natural products in vivo, but has rarely achieved the level of sustainability desired for medicinal applications. This approach is limited by our lack of understanding of biosynthesis and pathway expression. The focus of this dissertation is biosynthetic strategies for the supply of therapeutically-relevant natural products. Two examples are included, one involving a biosynthetic outlook of a known family of compounds with an uncharacterized metabolic origin, and a second uniting discovery, production, and biological characterization of a novel anti-HIV compound. The adociasulfates are a family of marine sponge-derived meroterpenes known to inhibit kinesin, making them attractive anticancer drug leads. Despite difficulties in synthesizing adociasulfates, biosynthesis has never been investigated as a potential means of production. In Chapter 1, detailed consideration is given to the biosynthetic origin of these compounds, revealing a set of just four possible precursors for all sponge merotriterpenes. The mechanism of action of adociasulfates, addressed in Chapter 2, was shown to occur in a 1:1 interaction with kinesin, contrary to previous reports of microtubule-mimicking aggregates. Adociasulfates are thus shown to be valuable tools for the study of kinesin and maintain potential therapeutic importance, making their production an ever more important goal. The discovery, production, and biological characterization of an anti-HIV lanthipeptide, divamide A, is described in Chapter 3. The divamides were discovered from small tunicates from Papua New Guinea. By integrating structure- and genomics-based methodologies, we were able to elucidate the structure of a small amount of isolated material. This approach also provided us with a biosynthetic platform from which heterologous expression and sustainable production were achieved in Escherichia coli. The structure activity relationships of the divamides show that functional diversity is achieved by introducing minor structural changes to a conserved chemical scaffold Finally, an extended family of related peptides was identified that bears some of the hallmarks of known diversity-generating pathways

Queensland University of Technology: Handbook 1999

The Queensland University of Technology handbook gives an outline of the faculties and subject offerings available that were offered by QUT

Queensland University of Technology: Handbook 1997

The Queensland University of Technology handbook gives an outline of the faculties and subject offerings available that were offered by QUT

Queensland University of Technology: Handbook 1996

The Queensland University of Technology handbook gives an outline of the faculties and subject offerings available that were offered by QUT

Queensland University of Technology: Handbook 1998

The Queensland University of Technology handbook gives an outline of the faculties and subject offerings available that were offered by QUT