Title

Nutritional studies on the production of the antibiotic platensimycin by Streptomyces platensis.

Date of Award

5-1-2014

Document Type

Thesis

School

College of Liberal Arts

Degree Name

Bachelor in Arts

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.