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| author | Maria Falzone |
| title | Nutritional Studies on the Production of the Antibiotic Platensimycin by Streptomyces platensis |
| abstract |
Given a recent lack of research and development of antibiotic compounds, there is a great need for new drugs (Fernandes 2006). Resistant pathogens are becoming more
prominent and are leading to an increasing number of infections that are difficult to cure (Jang et al. 2010). Platensimycin and platencin are two novel antibiotic
compounds that are natural products produced by the actinomycete Streptomyces platensis (Wang et al. 2006). These compounds operate by inhibiting bacterial fatty acid
synthesis, which is a novel and therefore uncommon antibiotic target. Platensimycin specifically inhibits the condensation-elongation enzyme FabF, and platencin is a
dual inhibitor of FabF and FabH, another condensation-elongation enzyme. These compounds are active against methicillin-resistant Staphylococcus aureus (MRSA),
vancomycin-resistant enterococci (VRE), as well as numerous other problematic pathogens (Singh et al. 2006). Unfortunately, they have shown very poor in vivo
pharmacokinetics and have not yet been marketed. Because of their method of action against fatty acid synthesis, they are an important lead in the current struggle
associated with antibiotic discovery and need for new antibiotic compounds. Efforts are being made to manipulate the structure of these compounds through natural
production and through chemical synthesis to potentially improve pharmacokinetics (Jang et al. 2010). Platensimycin has recently shown activity as a diabetes drug in
mouse models, making the study of these compounds even more important (Wu et al. 2011). In an effort to learn additional information about the biosynthetic pathways of
these compounds and their regulation as well as to develop an optimal production medium for S. platensis, we have engineered a soluble, chemically-defined production
medium from the original Merck and Co. complex, insoluble production medium (PM1). The chemically-defined production medium, PM7, contains g/L 30 glucose, 50 lactose,
5 MOPS (3-(N-morpholino)propanesulfonic acid) buffer, and 0.5 ammonium sulfate. We have also determined that aspartic acid and potassium chloride (KCl) are stimulatory
to antibiotic production when added to the production medium.
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| school | The College of Liberal Arts, Drew University |
| degree | B.A. (May 2014) |
| advisors | Dr. Adam Cassano
Dr. Arnold Demain |
| committee | Dr. Adam Cassano
Dr. Arnold Demain
Dr. Joanna Miller
Dr. James Carter |
| full text | MEFalzone.pdf |
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