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Abstract

Microbes have made a phenomenal contribution to the health and well-being of people throughout the world. In addition to producing many primary metabolites, such as amino acids, vitamins and nucleotides, they are capable of making secondary metabolites, which constitute half of the pharmaceuticals on the market today and provide agriculture with many essential products. This review centers on these beneficial secondary metabolites, the discovery of which goes back 80 years to the time when penicillin was discovered by Alexander Fleming.

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The European ban on growth-promoting antibiotics and emerging consequences for human and animal health.

Mark Casewell, Christian Friis, Enric Marco … (2003)

Following the ban of all food animal growth-promoting antibiotics by Sweden in 1986, the European Union banned avoparcin in 1997 and bacitracin, spiramycin, tylosin and virginiamycin in 1999. Three years later, the only attributable effect in humans has been a diminution in acquired resistance in enterococci isolated from human faecal carriers. There has been an increase in human infection from vancomycin-resistant enterococci in Europe, probably related to the increased in usage of vancomycin for the treatment of methicillin-resistant staphylococci. The ban of growth promoters has, however, revealed that these agents had important prophylactic activity and their withdrawal is now associated with a deterioration in animal health, including increased diarrhoea, weight loss and mortality due to Escherichia coli and Lawsonia intracellularis in early post-weaning pigs, and clostridial necrotic enteritis in broilers. A directly attributable effect of these infections is the increase in usage of therapeutic antibiotics in food animals, including that of tetracycline, aminoglycosides, trimethoprim/sulphonamide, macrolides and lincosamides, all of which are of direct importance in human medicine. The theoretical and political benefit of the widespread ban of growth promoters needs to be more carefully weighed against the increasingly apparent adverse consequences.

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Natural products in drug discovery and development.

G M Cragg, D Newman, K M Snader (1997)

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Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent.

O Hensens, J Hirshfield, K Hoogsteen … (1980)

Mevinolin, a fungal metabolite, was isolated from cultures of Aspergillus terreus. The structure and absolute configuration of mevinolini and its open acid form, mevinolinic acid, were determined by a combination of physical techniques. Mevinolin was shown to be 1,2,6,7,8,8a-hexahydro-beta, delta-dihydroxy-2,6-dimethyl-8-(2-methyl-1-oxobutoxy)-1-naphthalene-hepatanoic acid delta-lactone. Mevinolin in the hydroxy-acid form, mevinolinic acid, is a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase [mevalonate: NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34]; its Ki of 0.6 nM can be compared to 1.4 nM for the hydroxy acid form of the previously described related inhibitor, ML-236B (compactin, 6-demethylmevinolin). In the rat, orally administered sodium mevinolinate was an active inhibitor of cholesterol synthesis in an acute assay (50% inhibitory dose = 46 microgram/kg). Furthermore, it was shown that mevinolin was an orally active cholesterol-lowering agent in the dog. Treatment of dogs for 3 weeks with mevinolin at 8 mg/kg per day resulted in a 29.3 +/- 2.5% lowering of plasma cholesterol.

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PubMed ID:: 19132062

DOI:: 10.1038/ja.2008.16

ScienceOpen disciplines: Chemistry

Keywords: Animals,Anti-Bacterial Agents,chemical synthesis,history,pharmacology,Biological Products,chemistry,Drug Resistance, Bacterial,Drug Resistance, Fungal,Drug Resistance, Microbial,History, 20th Century,History, 21st Century,Humans

Microbial drug discovery: 80 years of progress.

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Abstract

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Drug_transporters

Most cited references 107

The European ban on growth-promoting antibiotics and emerging consequences for human and animal health.

Natural products in drug discovery and development.

Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent.

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Journal

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