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Showing 1 to 20 of 26 for “"natural product biosynthesis"”.
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Natural Product Biosynthesis In Uncultured Bacteria
… methods it is not possible to characterize the natural products encoded by the uncultured majority. The heterologous expression of biosynthetic gene clusters cloned from DNA extracted directly from environmental samples (eDNA) has begun to provide access to the chemical diversity encoded in the …
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Structure Determination of Natural Product Biosynthesis Enzymes
Natural products (NPs) frequently display elaborate molecular frameworks challenging biologists to ascertain the genetic origin and catalytic logic affording intricate NP biosynthesis. Beyond the basic research inspired by multiplicity of NPs discovered thus far, the biological activities …
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Flavin-dependent Enzymes in Natural Product Biosynthesis
Natural products are biologically active metabolites produced by fungi, bacteria, and plants that have an extended application in pharmaceutical and chemical industries. Because of their chemical versatility, flavoenzymes are commonly involved in natural product biosynthetic pathways. This has …
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Diverse enzyme reactions in phosphonate natural product biosynthesis
… biosynthetic gene clusters encoding phosphonate natural products have been characterized by mining of microbial genomes. Phosphonates, which are characterized by their hydrolytically stable carbon-phosphorus bond, are prevalent in everyday life, such as in commercially available herbicides and an …
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Enabling Natural Product Biosynthesis With Novel Synthetic Biology Tools
… several novel synthetic biology tools for natural product research and development. The first tool is DNA assembler, which allows rapid construction of large recombinant DNAs in a single-step fashion through yeast in vivo homologous recombination. Further applications of DNA assembler to …
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Investigations of metalloenzymes involved in bacterial natural product biosynthesis
Just as the structures of bacterial natural products have long been a source of inspiration for new developments in drug discovery and organic synthesis, so have investigations of their biosynthetic pathways led to the discovery of countless new enzyme-catalyzed reactions that open new frontiers of …
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A genomics-led approach to deciphering heterocyclic natural product biosynthesis
… biological processes and are widespread among natural products. Oxazole-containing natural products possess a broad range of bioactivities and are of great interest in the pharmaceutical and agrochemical industries. Herein, the biosynthetic routes to the oxazole-containing phthoxazolins and the …
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Functional Genomic Analysis of Natural Product Biosynthesis and Secretion in Aspergillus fumigatus
… pes1 was found to be involved in the biosynthesis of the conidial metabolite, fumigaclavine C, as this metabolite was absent in both A. fumigatus �akuB:�pes1 and �pes146645. In parallel studies, we identified a gene (gliK) responsible for gliotoxin biosynthesis and showed that gliK is …
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Revealing the molecular details of azoline formation in ribosomal natural product biosynthesis
… Encoded by many bacteria and archaea, these natural products occupy a large chemical and functional space and are linked by the presence of the eponymous azole moieties. Previous work has demonstrated that an evolutionarily conserved, heterotrimeric enzyme complex (TOMM synthetase) is …
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Investigations into the molecular basis of enzyme-catalyzed reactions in natural product biosynthesis
… of the enzymes responsible for the biosynthesis of these molecules will lead to a better understanding of specialized metabolism. In order to utilize these enzymes in a biotechnological setting, additional studies need to be performed on their substrate scopes and specificities. In …
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Structural and biochemical studies on enzymes involved in natural product biosynthesis and cellular respiration
Natural products have recently become an interest in modern research. This is due to their synthesis mainly by living organisms and their natural biosynthesis and abundance. Many of these compounds have been found to have pharmaceutical and industrial applications, and have been used as the basis …
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Rational Engineering of Expression Level of Multi-Gene Systems encoding Natural Product Biosynthesis in Streptomyces
… Next, we rationally optimize isoprenoid biosynthesis by perturbing relative expression of eight enzymes in the methylerythritol phosphate (MEP) pathway. One of the Design of Experiment (DoE) methods called Plackett-Burman design was used to guide the optimization effort for this …
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Genome mining for natural product biosynthesis: Amino acids, nonribosomal peptides, and ribosomal peptides with posttranslational modifications
Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2027-05-01
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Investigating and engineering the post-translational modifications in RiPP natural product biosynthesis (I) Thiopeptides (II) Sactipeptides
… metabolites from microbes have been a highly productive source of chemical matter that ultimately led to most of today’s clinically used antibiotics. Many of these natural products are derived from polyketide synthase (PKS) or non-ribosomal peptide synthetase (NRPS) families, including …
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Structural studies of S-adenosyl-L-methionine radical enzymes involved in tRNA and natural product biosynthesis
… enzymes that catalyze the key steps in the biosynthesis of the tRNA modified bases wybutosine and queuosine. TYWI catalyzes the formation of the characteristic imidazopurine ring of wybutosine through a disputed mechanism. Here, we have garnered support for one of the proposed mechanisms, …
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Mechanistic interrogations of ribosomal and non-ribosomal natural product enzymes
… proteins involved in metabolite regulation and natural product biosynthesis. In the first case, I will describe the structural basis for transcriptional regulation of a small molecule metabolite, p-coumarate, and the remaining cases involve enzymes responsible for biosyntheses of complex natural …
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Mass Spectrometric Studies of Nonribosomal, Enzymatic Assembly of Natural Products Through Thiotemplate Biosynthesis
… study of NRP/PKS enzymes for the elucidation of natural product biosynthesis. The reliance of FTMS will continue to improve and should prove itself worthy of the best analytical assay tool for uncovering the intricate mechanisms of thiotemplate enzymes.
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Investigation of the Discoipyrroles and Other Marine Bacteria Derived Natural Products
Natural products are a rich source of scientific innovation. These chemical compounds are canonically celebrated as biomedical tools or synthetic chemistry feats. Discovery of new chemical compounds has benefited from the study of natural product biosynthesis, or the methods by which they are …
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HARNESSING NATURE’S MACHINERY: CHARACTERIZATION OF BACTERIAL BIOSYNTHETIC ENZYMES FOR CHALLENGES IN ORGANIC SYNTHESIS
… and communicate using secondary metabolites, or natural products. This billion-year molecular “arms race” has enabled bacteria to biosynthesize complex molecules that are challenging for humans to access via traditional organic synthesis. This dissertation presents three distinct projects …
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Analysis and Engineering of Polyene Biosynthesis in Actinomycetes
… concerns the biosynthetic pathways to antibiotic natural products in actinomycete bacteria, and evaluates three different approaches to accessing novel chemical diversity from these pathways. In Chapter 1, major pathways of natural product biosynthesis in Streptomyces and allied bacteria are …
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