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      Microbial drug discovery: 80 years of progress

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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.
          Article 0 comments Cited 224 times – based on 0 reviews     Review now
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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.
              Article 0 comments Cited 147 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Arnold L Demain: ademain@drew.edu
                Journal
                Journal ID (nlm-ta): J Antibiot (Tokyo)
                Journal ID (iso-abbrev): J. Antibiot
                Title: The Journal of Antibiotics
                Publisher: Nature Publishing Group UK (London )
                ISSN (Print): 0021-8820
                ISSN (Electronic): 1881-1469
                Publication date (Electronic): 9 January 2009
                Publication date (Print): 2009
                Volume: 62
                Issue: 1
                Pages: 5-16
                Affiliations
                [1 ]GRID grid.255236.5, ISNI 0000 0001 2290 3196, Research Institute for Scientists Emeriti (RISE), Drew University, ; Madison, NJ USA
                [2 ]GRID grid.9486.3, ISNI 0000 0001 2159 0001, Departamento de Biología Molecular y Biotecnología, , Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), ; México, DF México
                Article
                Publisher ID: BFja200816
                DOI: 10.1038/ja.2008.16
                PMC ID: 7094699
                PubMed ID: 19132062
                SO-VID: 90922cd5-f423-47e7-aff7-47fbc7783f42
                Copyright © © Japan Antibiotics Research Association 2009
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Date received : 3 October 2008
                Date accepted : 15 November 2008
                Categories
                Subject: Article
                Custom metadata
                issue-copyright-statement © The Author(s) under exclusive licence to the Japan Antibiotics Research Association 2009

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: agricultural products,antibiotics,pharmaceuticals,resistance development
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: agricultural products, antibiotics, pharmaceuticals, resistance development

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