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Interests: Research in the Strauss group is broadly focused on increasing our understanding of the enzymology of coenzyme A (CoA) and other medicinally-relevant low molecular weight thiols, and applying this knowledge in biocatalysis, and in antibiotic drug development. Our goal is to identify new drug targets in important human pathogens such as Staphylococcus aureus, Mycobacterium tuberculosis and Plasmodium falciparum that exploit their dependence on these essential cofactors.

Our research strategy focuses on elucidating and studying the enzymes involved in the biosynthetic pathway of the thiol-containing cofactor, and applying this knowledge in the design of inhibitors of these enzymes, and those that use the cofactor. Often such inhibitors are also analogues of the native cofactor, and can be prepared biocatalytically by co-opting the natural biosynthetic enzymes. The figure below illustrates this strategy for CoA, although the same approach is currently being followed in studying mycothiol, the unique low molecular weight thiol of actinomycetes, which includes M. tuberculosis.

Tools: We use a broad range of tools and techniques in our laboratories, and you may expect to encounter people doing molecular biology, protein expression and purification, assay development, and also organic synthesis. Our labs are well-equipped to perform these studies, and we are heavy users of the university’s excellent MS facility which offers LC/MS and MALDI services.

Collaborations: We collaborate extensively with both national (most notably with the group of Dr. Anwar Jardine at the University of Cape Town) and international research groups in the US, Spain and Australia. Collaborations that have been especially fruitful, are those with the lab of Hong Zhang at the University of Texas Southwestern Medical Center in the US on the structural biology of pantothenate kinases, and with the group of Joaquín Ariño in Barcelona, Spain on coA biosynthesis in yeast. Currently we are exploring the structural biology of newly developed CoADR inhibitors with Al Claiborne (Wake Forest University) and Matt Redinbo (UNC Chapel Hill).

pathway elucidation

pathway inhibitors

biocatalysis

inhibitors of
cofactor utilization