Biosynthetic LEGO: enzymatic redesign to produce new vancomycin analogues. This project aims to uncover the reengineering potential of the biosynthetic machinery that produces glycopeptide antibiotics by advancing our understanding of how the core peptide production line functions. Natural product biosynthesis often produces complex peptide structures, with one important example being the glycopeptide antibiotics. This project expects to generate new knowledge about enzymatic peptide biosynthesi ....Biosynthetic LEGO: enzymatic redesign to produce new vancomycin analogues. This project aims to uncover the reengineering potential of the biosynthetic machinery that produces glycopeptide antibiotics by advancing our understanding of how the core peptide production line functions. Natural product biosynthesis often produces complex peptide structures, with one important example being the glycopeptide antibiotics. This project expects to generate new knowledge about enzymatic peptide biosynthesis using a highly interdisciplinary approach and previously developed tools. The anticipated outcomes of this project will be an enhanced understanding of how such complex peptide biosynthesis is performed, which is knowledge vital for future efforts to reengineer such biosynthetic peptide assembly lines as a series of modular LEGO blocks to produce new bioactive peptides.Read moreRead less
Defining peptide structure and function: the shape of things to come. In this project we develop new and general ways of chemically defining the structure and function of natural peptides. This then provides a basis of potential therapies to treat a number of diseases currently confronting Australia's aging population, for example, cataract, Alzheimer's disease, cancer, and cardiovascular disease.
Understanding the mechanisms of peptide cyclisation. This project aims to identify, study, engineer and apply a new class of biocatalysts (called asparaginyl endopeptidase enzymes) as versatile tools for manufacturing of advanced therapeutics and bio-insecticides. The expected outcomes include fundamental new knowledge on the mechanism of action of these catalysts, an expanded toolbox for precision engineering of biomolecules and new strategies for production of high-value pharmaceuticals and cr ....Understanding the mechanisms of peptide cyclisation. This project aims to identify, study, engineer and apply a new class of biocatalysts (called asparaginyl endopeptidase enzymes) as versatile tools for manufacturing of advanced therapeutics and bio-insecticides. The expected outcomes include fundamental new knowledge on the mechanism of action of these catalysts, an expanded toolbox for precision engineering of biomolecules and new strategies for production of high-value pharmaceuticals and crop protecting agents. The project is significant because it will contribute to high value biotechnology and agricultural industries in Australia, with the potential for economic, environmental, training and societal benefits.Read moreRead less
Protein oxidation induced by singlet oxygen and peroxyl radicals and its consequences. Protein oxidation is a major problem in the food, agricultural, pharmaceutical industries and plays a role in human disease. These deleterious processes result in considerable economic and health care costs. Photo-oxidation and peroxyl radical reactions, with singlet oxygen and peroxides as key intermediates, appear to be especially damaging. Quantitative and mechanistic data will be generated on the role of r ....Protein oxidation induced by singlet oxygen and peroxyl radicals and its consequences. Protein oxidation is a major problem in the food, agricultural, pharmaceutical industries and plays a role in human disease. These deleterious processes result in considerable economic and health care costs. Photo-oxidation and peroxyl radical reactions, with singlet oxygen and peroxides as key intermediates, appear to be especially damaging. Quantitative and mechanistic data will be generated on the role of readily oxidised side-chains (tryptophan, tyrosine, histidine, cysteine, cystine and methionine) in protein fragmentation, aggregation and secondary reactions, arising from side-chain peroxides, peroxyl and alkoxyl radicals. Understanding the sites of damage and reaction mechanisms is critical to the prevention of these processes.Read moreRead less