This thesis reports studies on the substrate specificity of crucial ketosynthase (KS) domains from trans-AT Polyketide Synthases (PKSs). Using a combination of electrospray ionisation-mass spectrometry (ESI-MS) and simple N-acetyl cysteamine (SNAC) substrate mimics, the specificity of a range of KS domains from the bacillaene and psymberin PKSs have been succsessfully studied with regard to the initial acylation step of KS-catalysis. In addition, the ability to alter the substrate tolerance of KS domains by simple point mutations in the active site has been demonstrated. A series of acyl-ACPs have been synthesised using a novel methodology and employed to probe the substrate specificity of both KS domains and the previously uncharcterised acyl hydrolase domain, PedC. KS-catalysed chain elongation reactions have also been conducted and monitored by ESI-MS/MS. All KS domains studied exhibited higher substrate specificity at the elongation step than in the preceeding acylation step. Furthermore, a mechanism of reversible acylation is proposed using the PsyA ACP1-KS1 di-domain. The findings in this thesis provide important insights into mechanisms of KS specificity and show that mutagenesis can be used to expand the repertoire of acceptable substrates for future PKS engineering.

Natural Products: Discourse, Diversity and Design provides an informative and accessible overview of discoveries in the area of natural products in the genomic era, bringing together advances across the kingdoms. As genomics data makes it increasingly clear that the genomes of microbes and plants contain far more genes for natural product synthesis than had been predicted from the numbers of previously identified metabolites, the potential of these organisms to synthesize diverse natural products is likely to be far greater than previously envisaged. Natural Products addresses not only the philosophical questions of the natural role of these metabolites, but also the evolution of single and multiple pathways, and how these pathways and products may be harnessed to aid discovery of new bioactives and modes of action. Edited by recognized leaders in the fields of plant and microbial biology, bioorganic chemistry and natural products chemistry, and with contributions from researchers at top labs around the world, Natural Products is unprecedented in its combination of disciplines and the breadth of its coverage. Natural Produces: Discourse, Diversity and Design will appeal to advanced students and experienced researchers, from academia to industry, in diverse areas including ecology, industrial biotechnology, drug discovery, medicinal chemistry, agronomy, crop improvement, and natural product chemistry.

This book highlights analytical chemistry instrumentation and practices applied to the analysis of natural products and their complex mixtures, describing techniques for isolating and characterizing natural products. • Applies analytical techniques to natural products research – an area of critical importance to drug discovery • Offers a one-stop shop for most analytical methods: x-ray diffraction, NMR analysis, mass spectrometry, and chemical genetics • Includes coverage of natural products basics and highlights antibacterial research, particularly important as efforts to combat drug resistance gain prominence • Covers instrumental techniques with enough detail for both current practitioners and beginning researchers

Comprehensive Natural Products III, Third Edition, Seven Volume Set updates and complements the previous two editions, including recent advances in cofactor chemistry, structural diversity of natural products and secondary metabolites, enzymes and enzyme mechanisms and new bioinformatics tools. Natural products research is a dynamic discipline at the intersection of chemistry and biology concerned with isolation, identification, structure elucidation, and chemical characteristics of naturally occurring compounds such as pheromones, carbohydrates, nucleic acids and enzymes. This book reviews the accumulated efforts of chemical and biological research to understand living organisms and their distinctive effects on health and medicine and to stimulate new ideas among the established natural products community. Provides readers with an in-depth review of current natural products research and a critical insight into the future direction of the field Bridges the gap in knowledge by covering developments in the field since the second edition published in 2010 Split into 7 sections on key topics to allow students, researchers and professionals to find relevant information quickly and easily Ensures that the knowledge within is easily understood by and applicable to a large audience

There is a large market demand for new drugs. The existing chronic or common ailments without cures, development of new diseases with unknown causes, and the widespread existence of antibiotic-resistant pathogens, have driven this field of research further by looking at all potential sources of natural products. To date, microbes have made a significant contribution to the health and well-being of people globally. The discoveries of useful metabolites produced by microbes have resulted in a significant proportion of pharmaceutical products in today’s market. Therefore, the investigation and identification of bioactive compound(s) producing microbes is always of great interest to researchers. Actinobacteria are one of the most important and efficient groups of natural metabolite producers. Among the numerous genera, Streptomyces have been recognized as prolific producers of useful natural compounds, as they provide more than half of the naturally-occurring antibiotics isolated to-date and continue to emerge as the primary source of new bioactive compounds. Certainly, these potentials have attracted ample research interest and a wide range of biological activities have been subsequently screened by researchers with the utilization of different In vitro and In vivo model of experiments. Literature evidence has shown that a significant number of interesting compounds produced by Actinobacteria were exhibiting either strong anticancer or neuroprotective activity. The further in depth studies have then established the modulation of apoptotic pathway was involved in those observed bioactivities. These findings indirectly prove the biopharmaceutical potential possessed by Actinobacteria and at the same time substantiate the importance of diverse pharmaceutical evaluations on Actinobacteria. In fact, many novel compounds discovered from Actinobacteria with strong potential in clinical applications have been developed into new drugs by pharmaceutical companies. Together with the advancement in science and technology, it is predicted that there would be an expedition in discoveries of new bioactive compounds producing Actinobacteria from various sources, including soil and marine sources. In light of these current needs, and great interest in the scope of this research, this book seeks to contribute on the investigation of different biological active compound(s) producing actinobacteria which are exhibiting antimicrobial, antioxidant, neuroprotective, anticancer activities and similar.