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Showing 1 to 20 of 30 for “"isoprenoid biosynthesis"”.
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Targeting isoprenoid biosynthesis for drug discovery
… resistance, there is a need for new drugs, and isoprenoid biosynthesis is an attractive target for drug discovery. In chapter 1, I briefly introduce the isoprenoid biosynthesis pathway and two important drug targets: a trans-prenyl transferase farnesyl diphosphate synthase (FPPS), and a …
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Mechanism, inhibition and spectroscopy of isoprenoid biosynthesis enzymes
Isoprenoids (or terpenes) are a large class of compounds with great physiological importance in all kingdoms of life. The research in this work explored the mechanism and inhibition of several enzymes in two important pathways for isoprenoid biosynthesis. The first pair of enzyme are IspG and IspH, …
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Experimental and Computational Study of Bisphosphonates Targeting Isoprenoid Biosynthesis Pathway
Bisphosphonates are a class of drugs widely used to treat bone resorption diseases. Recently, bisphosphonates have been found to have anti-cancer, anti-parasitic, anti-bacterial and herbicidal activity. They also have the unexpected property of activating human gammadelta T cells to kill tumor …
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Isoprenoid Biosynthesis Pathway as a Drug Target for Bisphosphonates: Transcriptional Profile Investigation
Bisphosphonates are known as potent inhibitors of the enzyme farnesyl diphosphate synthase (FPPS) and are clinically used to treat bone related disorders such as osteoporosis and bone cancer. Here we describe the development, testing and study of the mechanism of action of novel bisphosphonates as …
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Enzymes as Drug Targets in the Isoprenoid Biosynthesis Pathway: Structure, Mechanism and Inhibition
Enzymes in isoprenoid biosynthesis pathway play important roles in all living organisms. Several of them have been identified as drug targets. Here we reported the inhibition study of isopentenyl diphosphate/dimethylallyl diphosphate isomerase (IPPI) and deoxyzylolus reductoisomerase (DXR), along …
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Kinetic and structural studies on the first three enzymes in Bacillus anthracis isoprenoid biosynthesis.
… on the first three enzymes in Bacillus anthracis isoprenoid biosynthesis.
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Gene expression and biochemistry of isoprenoid biosynthesis in the glandular secretory trichomes of Artemisia annua
… understand the genes involved in terpenoid biosynthesis in A. annua, the full length sequence of a short chain alcohol dehydrogenase highly represented in an expressed sequence tag library and shown to have trichome-specific expression by RT-PCR, was cloned. Heterologous expression in …
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Structure, function and inhibition of GcpE, FPPS and GGPPS: targeting isoprenoid biosynthesis for drug discovery
… synthase (GGPPS) are enzymes involved in isoprenoid biosynthesis. Most bacterial IspGs contain two domains: a TIM barrel (A) and a 4Fe4S domain (B), but in plants and malaria parasites there is a large insert domain (A*) whose structure and function are unknown. We show bacterial IspGs …
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Mechanisms of action and inhibition of [4Fe-4S] proteins IspG and IspH in isoprenoid biosynthesis
… (also known as the non-mevalonate pathway) of isoprenoid biosynthesis is potentially an important anti-bacterial and anti-malarial drug target. However, the catalytic mechanisms of the last two enzymes in this pathway, IspG (also known as GcpE) and IspH (also known as LytB) were largely …
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Engineering a novel pathway for isoprenoid synthesis
Isoprenoids comprise a large class of chemicals, of significant interest due to their diverse properties. Most isoprenoids are plant secondary metabolites and are of commercial importance due to their varied applications in fields spanning medicine, agriculture, flavors, fragrances, cosmetics and …
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Targeting isoprenoid and quinone biosynthesis for antimicrobial discovery
"Enzymes in isoprenoid biosynthesis pathway play important roles in all living organisms. Here we report the first structure of heptaprenyl diphosphate synthase from Staphylococcus aureus (SaHepPPS) together with an investigation of its mechanism of action, and inhibition. HepPPS is involved in …
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Directed Evolution of Phosphite Dehydrogenase and Engineered Biosynthesis of Fr-900098
… be used to inhibit the nonmevalonate pathway for isoprenoid biosynthesis in the malaria-causing parasite Plasmodium falciparum. Although no biosynthetic pathway for fosmidomycin has been elucidated as of yet, the biosynthetic pathway for FR-900098 has been cloned from Streptomyces rubellomurinus …
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Genetic Dissection of Heart Development in the Fruit Fly Drosophila Melanogaster
… thus representing an endpoint of isoprenoid biosynthesis. These findings reveal a cardial cell-autonomous requirement of Ggamma 1 geranylgeranylation for heart formation and suggest the involvement of the mevalonate pathway in congenital heart disease. In addition, we found that …
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Structure and function of the terpene biosynthesis enzyme, IspH
… reductase, is an essential enzyme in isoprenoid biosynthesis and an important drug/herbicide target. The main research in this work investigated the structures and functions of IspHs from various organisms. Using a sequence similarity network we found that some IspHs form …
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Applications of Solid State Nuclear Magnetic Resonance Spectroscopy as a Tool for Structure Based Drug Design
… which forms farnesyl diphosphate in the isoprenoid biosynthesis pathway, is an exciting new drug target because of its central role in a diverse array of biochemical pathways. Farnesyl diphosphate is a precursor in the synthesis of sterols, ubiquinones, dolichol, heme A, and a variety of …
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Molecular target identification of antimalarial drugs using proteomic and metabolomic approaches
… are urgently needed. Purine and pyrimidine biosynthesis for DNA and RNA synthesis has been recognized as a source of therapeutic targets. Targeted metabolite profiling has aided in the understanding of several biological processes in the parasite besides drug discovery. Therefore, having a …
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Genetic Engineering of Plant Seeds to Increase Thiamin (Vitamin B1) Content
… cycle, pentose phosphate pathway, Calvin cycle, isoprenoid biosynthesis, and branched-chain amino acid biosynthesis. All living organisms need thiamine. However, human and animals can synthesize TPP from thiamine, but they are not able to synthesize thiamine de novo. Therefore, human and animals …
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Rational Engineering of Expression Level of Multi-Gene Systems encoding Natural Product Biosynthesis in Streptomyces
… assembly pipeline. 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 …
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Toward the synthesis and evaluation of novel N-acylated FR-900098 analogs
… a necessary enzyme in Plasmodium for isoprenoid biosynthesis via the non-mevalonate pathway, which does not exist in humans. Although FR-900098 was determined to be about twice as potent as fosmidomycin, it is important to note that, as a Streptomycete secondary metabolite, it is by no …
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MMV008138 and analogs: potential novel antimalarial agents for P. falciparum
… P. falciparum parasites synthesize essential isoprenoid precursors, isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), via a non-mevalonate pathway: the methylerythritol phosphate (MEP) pathway. This pathway is not utilized by humans. Thus, compounds that target the MEP …
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