Student Theses and Dissertations

Date of Award


Document Type


RU Laboratory

Darst Laboratory


sporulation, bacillus, Geobacillus stearothermophilus, sporulation histidine kinase


The microbial world is rich with complexity. Bacteria have evolved several mechanisms to help them survive the harshest environments on earth. These range from complex developmental transformations to the synthesis of small molecule antibiotics that can fend off competing species. Both of these topics will be the focus of this thesis, specifically the regulation of endospore formation in Bacillus and the generation of a sulfated small molecule antibiotic from an uncultured soil bacterium. Using standard molecular biology methods and the techniques of X-ray crystallography, synthetic chemistry, and protein semisynthesis, we have: (1) Solved the X-ray crystal structure of a Geobacillus stearothermophilus sporulation histidine kinase in complex with an inhibitor of the kinase reaction (Chapter 2). (2) Developed an approach using the methods of protein semisynthesis and small molecule organic chemistry that will facilitate the study of active state conformations of a sporulation histidine kinase (Chapter 3). (3) Developed a full-length sporulation histidine kinase expression and purification system so that we may gain insights into the signaling mechanism of these proteins through crystallography (Chapter 4). (4) Developed an expression and purification system for an important stage II sporulation protein for future crystallographic studies (Chapter 5). (5) Solved the X-ray crystal structures of two sulfotransferases from an uncultured soil bacterium in complex with the antibiotic teicoplanin (Chapters 6 and 7).


A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy.

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