Pyoluteorin Biosynthesis Copy
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Pyoluteorin Biosynthesis Copy
Pyoluteorin is a natural antibiotic that is biosynthesized from a hybrid nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) pathway. Pyoluteorin was first isolated in the 1950s from '' Pseudomonas aeruginosa'' strains T359 and IFO 3455 and was found to be toxic against oomycetes, bacteria, fungi, and against certain plants. Pyoluteorin is most notable for its toxicity against the oomycete ''Pythium ultimum'', which is a plant pathogen that causes a global loss in agriculture. Currently, pyoluteorin derivatives are being studied as an Mcl-1 antagonist in order to target cancers that have elevated Mcl-1 levels. Biosynthesis Pyoluteorin is synthesized from an NRPS/PKS hybrid pathway. The resorcinol ring is derived from a type I PKS while the dichloropyrrole moiety is derived from a type II NRPS. Pyoluteorin biosynthesis begins with the activation of L-proline to prolyl-AMP by the adenylation domain PltF. With prolyl-AMP still in the active site, the ...
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Antibiotic
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the common cold or influenza; drugs which inhibit viruses are termed antiviral drugs or antivirals rather than antibiotics. Sometimes, the term ''antibiotic''—literally "opposing life", from the Greek roots ἀντι ''anti'', "against" and βίος ''bios'', "life"—is broadly used to refer to any substance used against microbes, but in the usual medical usage, antibiotics (such as penicillin) are those produced naturally (by one microorganism fighting another), whereas non-antibiotic antibacterials (such as sulfonamides and antiseptics) ...
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Cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss, and a change in bowel movements. While these symptoms may indicate cancer, they can also have other causes. Over 100 types of cancers affect humans. Tobacco use is the cause of about 22% of cancer deaths. Another 10% are due to obesity, poor diet, lack of physical activity or excessive drinking of alcohol. Other factors include certain infections, exposure to ionizing radiation, and environmental pollutants. In the developing world, 15% of cancers are due to infections such as ''Helicobacter pylori'', hepatitis B, hepatitis C, human papillomavirus infection, Epstein–Barr virus and human immunodeficiency virus (HIV). These factors act, at least partly, by changing the genes of ...
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Biosynthesis
Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. This process often consists of metabolic pathways. Some of these biosynthetic pathways are located within a single cellular organelle, while others involve enzymes that are located within multiple cellular organelles. Examples of these biosynthetic pathways include the production of lipid membrane components and nucleotides. Biosynthesis is usually synonymous with anabolism. The prerequisite elements for biosynthesis include: precursor compounds, chemical energy (e.g. ATP), and catalytic enzymes which may require coenzymes (e.g.NADH, NADPH). These elements create monomers, the building blocks for macromolecules. Some important biological macromolecules include: proteins, which are composed of amino acid monomers joined via peptide bon ...
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Antibiotics
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the common cold or influenza; drugs which inhibit viruses are termed antiviral drugs or antivirals rather than antibiotics. Sometimes, the term ''antibiotic''—literally "opposing life", from the Greek roots ἀντι ''anti'', "against" and βίος ''bios'', "life"—is broadly used to refer to any substance used against microbes, but in the usual medical usage, antibiotics (such as penicillin) are those produced naturally (by one microorganism fighting another), whereas non-antibiotic antibacterials (such as sulfonamides and antisep ...
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Pyoluteorin Biosynthesis Copy
Pyoluteorin is a natural antibiotic that is biosynthesized from a hybrid nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) pathway. Pyoluteorin was first isolated in the 1950s from '' Pseudomonas aeruginosa'' strains T359 and IFO 3455 and was found to be toxic against oomycetes, bacteria, fungi, and against certain plants. Pyoluteorin is most notable for its toxicity against the oomycete ''Pythium ultimum'', which is a plant pathogen that causes a global loss in agriculture. Currently, pyoluteorin derivatives are being studied as an Mcl-1 antagonist in order to target cancers that have elevated Mcl-1 levels. Biosynthesis Pyoluteorin is synthesized from an NRPS/PKS hybrid pathway. The resorcinol ring is derived from a type I PKS while the dichloropyrrole moiety is derived from a type II NRPS. Pyoluteorin biosynthesis begins with the activation of L-proline to prolyl-AMP by the adenylation domain PltF. With prolyl-AMP still in the active site, the ...
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Thioesterase
Thioesterases are enzymes which belong to the esterase family. Esterases, in turn, are one type of the several hydrolases known. Thioesterases exhibit esterase activity (splitting of an ester into acid and Alcohol (chemistry), alcohol, in the presence of water) specifically at a thiol group. Thioesterases or thiolester hydrolases are identified as members of EC 3.1.2. Family The thioesterase activity is performed by members of the acyl-CoA thioesterase (ACOT) family. The regulatory role of ACOT in fatty acid metabolism depends on their substrate (biology), substrate specificity, tissue expression and subcellular localization. For example, deactivation of fatty acids at the ER may traffic fatty acids away from pathways associated with the ER membrane, such as glycerolipid biosynthesis. Two structurally different ACOT types lead to a similar enzymatic activity in vitro, dividing the family into type I and type II ACOTs. Type I ACOTs (ACOT1–6) contain the α/β-hydrolase domain, w ...
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Cyclic Compound
A cyclic compound (or ring compound) is a term for a compound in the field of chemistry in which one or more series of atoms in the compound is connected to form a ring. Rings may vary in size from three to many atoms, and include examples where all the atoms are carbon (i.e., are carbocycles), none of the atoms are carbon (inorganic cyclic compounds), or where both carbon and non-carbon atoms are present (heterocyclic compounds). Depending on the ring size, the bond order of the individual links between ring atoms, and their arrangements within the rings, carbocyclic and heterocyclic compounds may be aromatic or non-aromatic; in the latter case, they may vary from being fully saturated to having varying numbers of multiple bonds between the ring atoms. Because of the tremendous diversity allowed, in combination, by the valences of common atoms and their ability to form rings, the number of possible cyclic structures, even of small size (e.g., < 17 total atoms) numbers in the many b ...
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Monomer
In chemistry, a monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network in a process called polymerization. Classification Monomers can be classified in many ways. They can be subdivided into two broad classes, depending on the kind of the polymer that they form. Monomers that participate in condensation polymerization have a different stoichiometry than monomers that participate in addition polymerization: : Other classifications include: *natural vs synthetic monomers, e.g. glycine vs caprolactam, respectively *polar vs nonpolar monomers, e.g. vinyl acetate vs ethylene, respectively *cyclic vs linear, e.g. ethylene oxide vs ethylene glycol, respectively The polymerization of one kind of monomer gives a homopolymer. Many polymers are copolymers, meaning that they are derived from two different monomers. In the case of condensation polymerizations, the r ...
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Sylvie Garneau-Tsodikova
Sylvie Garneau-Tsodikova is a French Canadian-American chemist who is a Professor and Associate Vice President for Research at the University of Kentucky. One of the areas of her research interest is the development of new molecules to combat bacterial and fungal resistance. Early life and education Garneau-Tsodikova was born in Quebec City, Canada. She attended the Université Laval for her undergraduate studies in chemistry, where she graduated top of the class. As a student, she was honoured with several awards, including distinguishments from the Chemical Institute of Canada and Natural Sciences and Engineering Research Council. She completed a Master's thesis on the synthesis of glutamyl transfer RNA synthetase inhibitors. She moved to the University of Alberta for graduate studies, where she worked on the impact of antimicrobial agents of bacterial cell walls. During her doctoral studies she became interested in infectious diseases and the development of antibacter ...
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Halogenation
In chemistry, halogenation is a chemical reaction that entails the introduction of one or more halogens into a compound. Halide-containing compounds are pervasive, making this type of transformation important, e.g. in the production of polymers, drugs. This kind of conversion is in fact so common that a comprehensive overview is challenging. This article mainly deals with halogenation using elemental halogens (F2, Cl2, Br2, I2). Halides are also commonly introduced using salts of the halides and halogen acids. Many specialized reagents exist for and introducing halogens into diverse substrates, e.g. thionyl chloride. Organic chemistry Several pathways exist for the halogenation of organic compounds, including free radical halogenation, ketone halogenation, electrophilic halogenation, and halogen addition reaction. The nature of the substrate determines the pathway. The facility of halogenation is influenced by the halogen. Fluorine and chlorine are more electrophilic and are m ...
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Dehydrogenase
A dehydrogenase is an enzyme belonging to the group of oxidoreductases that oxidizes a substrate by reducing an electron acceptor, usually NAD+/NADP+ or a flavin coenzyme such as FAD or FMN. Like all catalysts, they catalyze reverse as well as forward reactions, and in some cases this has physiological significance: for example, alcohol dehydrogenase catalyzes the oxidation of ethanol to acetaldehyde in animals, but in yeast it catalyzes the production of ethanol from acetaldehyde. IUBMB Classification Oxidoreductases, enzymes that catalyze oxidation-reduction reactions, constitute Class EC 1 of the IUBMB classification of enzyme-catalyzed reactions. Any of these may be called dehydrogenases, especially those in which NAD+ is the electron acceptor (oxidant), but reductase is also used when the physiological emphasis on reduction of the substrate, and oxidase is used ''only'' when O2 is the electron acceptor. The systematic name of an oxidoreductase is "donor:acceptor oxidore ...
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Adenylylation
Adenylylation, more commonly known as AMPylation, is a process in which an adenosine monophosphate (AMP) molecule is covalently attached to the amino acid side chain of a protein. This covalent addition of AMP to a hydroxyl side chain of the protein is a posttranslational modification. Adenylylation involves a phosphodiester bond between a hydroxyl group of the molecule undergoing adenylylation, and the phosphate group of the adenosine monophosphate nucleotide (i.e. adenylic acid). Enzymes that are capable of catalyzing this process are called AMPylators. The known amino acids to be targeted in the protein are tyrosine and threonine, and sometimes serine. When charges on a protein undergo a change, it affects the characteristics of the protein, normally by altering its shape via interactions of the amino acids which make up the protein. AMPylation can have various effects on the protein. These are properties of the protein like, stability, enzymatic activity, co-factor binding, and ...
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