Aminoshikimate Pathway
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Aminoshikimate Pathway
The Aminoshikimate pathway is a biochemical pathway present in some plants, which has been studied by biologists, biochemists and especially those interested in manufacture of novel antibiotic drugs. The pathway is a novel variation of the shikimate pathway. The aminoshikimate pathway was first discovered and studied in the rifamycin B producer ''Amycolatopsis mediterranei''. Its end product, 3-amino-5-hydroxybenzoate, serves as an initiator for polyketide synthases in the biosynthesis of ansamycins. Overview Floss and coworkers identified the gene cluster associated with the aminoshikimate pathway in ''Amycolatopsis mediterranei''. The enzyme-catalyzed condensation of 1-deoxy-1-imino-D-erythrose 4-phosphate with phosphoenolpyruvate to form 4-amino-3,4-dideoxy-d-arabino-heptulosonic acid 7-phosphate has been proposed to be the first committed step in the aminoshikimate pathway. Guo and Frost demonstrated that the unusual metabolite, 1-deoxy-1-imino-D-erythrose 4-phosphate, is derive ...
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Shikimate
Shikimic acid, more commonly known as its anionic form shikimate, is a cyclohexene, a cyclitol and a cyclohexanecarboxylic acid. It is an important biochemical metabolite in plants and microorganisms. Its name comes from the Japanese flower ''shikimi'' (, the Japanese star anise, ''Illicium anisatum''), from which it was first isolated in 1885 by Johan Fredrik Eykman. The elucidation of its structure was made nearly 50 years later. Biosynthesis Phosphoenolpyruvate and erythrose-4-phosphate condense to form 3-deoxy-D-arabinoheptulosonate-7-phosphate (DAHP), in a reaction catalyzed by the enzyme DAHP synthase. DAHP is then transformed to 3-dehydroquinate (DHQ), in a reaction catalyzed by DHQ synthase. Although this reaction requires nicotinamide adenine dinucleotide (NAD) as a cofactor, the enzymic mechanism regenerates it, resulting in the net use of no NAD. : DHQ is dehydrated to 3-dehydroshikimic acid by the enzyme 3-dehydroquinate dehydratase, which is reduced to shi ...
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Rifamycin
The rifamycins are a group of antibiotics that are synthesized either naturally by the bacterium ''Amycolatopsis rifamycinica'' or artificially. They are a subclass of the larger family of ansamycins. Rifamycins are particularly effective against mycobacteria, and are therefore used to treat tuberculosis, leprosy, and mycobacterium avium complex (MAC) infections. The rifamycin group includes the "classic" rifamycin drugs as well as the rifamycin derivatives rifampicin (or rifampin), rifabutin, rifapentine, rifalazil and rifaximin. Rifamycin, sold under the trade name Aemcolo, is approved in the United States for treatment of travelers' diarrhea in some circumstances. Bacterium ''Streptomyces mediterranei'' was first isolated in 1957 from a soil sample collected near the beach-side town of St Raphael in southern France. The name was originally given by two microbiologists working with the Italian drug company Group Lepetit SpA in Milan, the Italian Grazia Beretta, and Pinh ...
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Amycolatopsis
''Amycolatopsis'' is a genus of high GC-content bacteria within the family Pseudonocardiaceae. The genus is known for producing many types of antibiotics, including * Epoxyquinomicin, related to ''Amycolatopsis sulphurea'', are a class of weak antibiotic and anti-inflammatory agent. *Vancomycin, obtained from ''Amycolatopsis orientalis'', is being used for infections resistant to other antibiotics. *Ristocetin, made by ''Amycolatopsis lurida'', was an antibiotic but ceased to apply due to adverse effects of platelet agglutination. Now it is used to assay von Willebrand disease. Degradation of bio-polymers Several bacteria from the genus ''Amycolatopsis'' are able to enzymatically hydrolyze the ester bonds of poly-lactic acid (PLA) films in aquatic medium. So far, it is one of the few known bacteria able to biodegrade the bioplastic outside compost facilities in a relatively short period of time. Species ''Amycolatopsis'' comprises the following species: * '' A. acidicola'' ...
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Ansamycin
Ansamycins is a family of bacterial secondary metabolites that show antimicrobial activity against many Gram-positive and some Gram-negative bacteria, and includes various compounds, including streptovaricins and rifamycins. In addition, these compounds demonstrate antiviral activity towards bacteriophages and poxviruses. Structure They are named ansamycins (from the Latin ansa, ''handle'') because of their unique structure, which consists of an aromatic moiety bridged by an aliphatic chain. The main difference between various derivatives of ansamycins is the aromatic moiety, which can be a naphthalene ring or a naphthoquinone ring as in rifamycin and the naphthomycins. Another variation consists of benzene or a benzoquinone ring system as in geldanamycin or ansamitocin. Ansamycins were first discovered in 1959 by Sensi et al. from ''Amycolatopsis mediterranei'', an actinomycete bacterium. Examples Rifamycins are a subclass of ansamycins with high potency against mycobact ...
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Aminoshikimate Pathway
The Aminoshikimate pathway is a biochemical pathway present in some plants, which has been studied by biologists, biochemists and especially those interested in manufacture of novel antibiotic drugs. The pathway is a novel variation of the shikimate pathway. The aminoshikimate pathway was first discovered and studied in the rifamycin B producer ''Amycolatopsis mediterranei''. Its end product, 3-amino-5-hydroxybenzoate, serves as an initiator for polyketide synthases in the biosynthesis of ansamycins. Overview Floss and coworkers identified the gene cluster associated with the aminoshikimate pathway in ''Amycolatopsis mediterranei''. The enzyme-catalyzed condensation of 1-deoxy-1-imino-D-erythrose 4-phosphate with phosphoenolpyruvate to form 4-amino-3,4-dideoxy-d-arabino-heptulosonic acid 7-phosphate has been proposed to be the first committed step in the aminoshikimate pathway. Guo and Frost demonstrated that the unusual metabolite, 1-deoxy-1-imino-D-erythrose 4-phosphate, is derive ...
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Aminoshikimic Acid
Aminoshikimic acid is a synthetic crystalline carboxylic acid. It is characterized by multiple stereogenic centers and functional groups arrayed around a six-membered carbocyclic ring. Aminoshikimic acid is also an alternative to shikimic acid as a starting material for the synthesis of neuraminidase inhibitors such as the antiinfluenza agent oseltamivir (Tamiflu). History Aminoshikimic acid is an unnatural carbohydrate, although aminoshikimic acid is the namesake of the aminoshikimate pathway, which generates the 3-amino-5-hydroxybenzoic acid (AHBA) starter unit required for the biosynthesis of the ansamycins and mitomycin The mitomycins are a family of aziridine-containing natural products isolated from ''Streptomyces caespitosus'' or ''Streptomyces lavendulae.'' They include mitomycin A, mitomycin B, and mitomycin C. When the name mitomycin occurs alone, it usually ...s. The first microbe-catalyzed syntheses of aminoshikimic acid were described by Guo and Frost in 2004. Pharm ...
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Oseltamivir
Oseltamivir, sold under the brand name Tamiflu, is an antiviral medication used to treat and prevent influenza A and influenza B, viruses that cause the flu. Many medical organizations recommend it in people who have complications or are at high risk of complications within 48 hours of first symptoms of infection. They recommend it to prevent infection in those at high risk, but not the general population. The Centers for Disease Control and Prevention (CDC) recommends that clinicians use their discretion to treat those at lower risk who present within 48 hours of first symptoms of infection. It is taken by mouth, either as a pill or liquid. Recommendations regarding oseltamivir are controversial as are criticisms of the recommendations. A 2014 Cochrane Review concluded that oseltamivir does not reduce hospitalizations, and that there is no evidence of reduction in complications of influenza. Two meta-analyses have concluded that benefits in those who are otherwise healthy do n ...
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