GROUP LEADER: Prof Erick Strauss
Position: Associate Professor
Office: A123 JC Smuts Building
PhD, Cornell University (USA), 2003
Beckman-Coulter Silver Medal, South African Society for Biochemistry and Molecular Biology (2010)
NRF President’s Award (P-rating) (2008-2012)
Rector’s Award for Outstanding Teaching, Stellenbosch University (2007)
Chemical Biology, Mechanistic Enzymology, Drug Design & Discovery, Biocatalysis
The Strauss Lab’s core research efforts are in the multidisciplinary field of Chemical Biology. We mainly focus on the chemistry and biology of the ubiquitous metabolic cofactor Coenzyme A, and on low molecular weight thiol-dependent redox biology. We also apply the expertise we gain in this manner to the design and development of new antibiotic agents – especially those that target diseases relevant in the African health context.
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 all aspects 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, which can be prepared biocatalytically by co-opting the natural biosynthetic enzymes, or which does this naturally as part of the inhibition strategy as shown for the natural product CJ-15,801 in the figure below. A similar approach is currently being investigated 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, Italy 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), and the preparation of novel thioglycoligases with Marco Moracci’s group at the CNR-IPB in Naples, Italy.
The Antibiotic CJ-15,801 is an Antimetabolite which Hijacks and then Inhibits CoA Biosynthesis. R. van der Westhuyzen, J.C. Hammons, J.L. Meier, S. Dahesh, W.J.A. Moolman, S.C. Pelly, V. Nizet, M.D. Burkart and E. Strauss. Chem. Biol. 19, 559–571 (2012).
Functional Mapping of the Disparate Activities of the Yeast Moonlighting Protein Hal3. J.A. Abrie, A. González, E. Strauss and J. Ariño. Biochem. J. 442, 357-368 (2012).
Grand challenge commentary: Exploiting single-cell variation for new antibiotics. E. Strauss. Nat. Chem. Biol. 6, 873–875, (2010).
Biocatalytic Production of Coenzyme A Analogues. E. Strauss, M. de Villiers and I. Rootman. ChemCatChem 2, 929-937, (2010).
Michael acceptor-containing coenzyme A analogues as inhibitors of the atypical coenzyme A disulfide reductase from Staphylococcus aureus. R. van der Westhuyzen and E. Strauss. J. Am. Chem. Soc. 132, 12853-12855 (2010).
3-Fluoroaspartate and Pyruvoyl-Dependent Aspartate Decarboxylase: Exploiting the Unique Characteristics of Fluorine to Probe Reactivity and Binding. J. de Villiers, L. Koekemoer and E. Strauss. Chem. Eur. J. 16, 10030-10041, (2010).
Moonlighting proteins Hal3 and Vhs3 form a heteromeric PPCDC with Ykl088w in yeast CoA biosynthesis. A. Ruiz, A. González, I. Muñoz, R. Serrano, J.A. Abrie, E. Strauss, and J. Ariño. Nature Chem. Biol. 5, 920-928, (2009).