Department of Chemistry

Rajesh Viswanathan

Assistant Professor

216.368.3696      nathan@case.edu      Millis 214

Viswanathan Research Group Site »


Interests: Organic Chemistry, Protein Biochemistry, Chemical Biology, Chemical Synthesis and Characterization, Genetically-Encoded Natural Products, Molecular Biology, Microbial Genetics, Bioinformatics, Metabolic Pathways, Drug Discovery

Bachelor of Science (B. Sc): Madras University (The New College), Chennai, India, 1994 – 1997.
Master of Science (M. Sc): Indian Institute of Technology, Kanpur, India, 1997 – 1999.
Ph.D. Indiana University, Bloomington, 1999 – 2005.
Post-Doctoral Research, University of Utah, 2005 – 2008.


Teaching at Case Western Reserve University

Fall 2008      Synthetic Methods in Organic Chemistry (CHEM 435)
Spring 2009      Advanced Organic Chemistry II (CHEM 422)
Fall 2009      Complex Molecular Synthesis (CHEM 436)
Spring 2010      Advanced Organic Chemistry II (CHEM 422)
Fall 2010      Synthetic Methods in Organic Chemistry (CHEM 435)
Fall 2011      Introductory Organic Chemistry Laboratory I (CHEM 233)
Spring 2012      Introductory Organic Chemistry Laboratory II (CHEM 234)
Fall 2012      Synthetic Methods in Organic Chemistry (CHEM 435)


Research Projects in Viswanathan Group




Natural Product Biosynthetic Pathways from Cyanobacteria


    
Figure 1. Left - Genomes in Tree of Life assembled by Joint Genome Institute. Cyanobacteria are a growing portion of the tree. Right - Our approach for studying biosynthetic pathways. Click the images for larger versions.


Through 3.5 billion years of evolution, cyanobacteria continue to shape our planet’s biodiversity while serving as repositories of bioactive compounds. In Nature’s repositories of biodiversity (see Figure 1, top) cyanobacteria occupy a rapidly growing space as more genomic data become available. While marine cyanobacteria have been elegantly studied for natural product pathway research, terrestrial Group V cyanobacteria (filamentous and from soil) remain largely underexplored for their biosynthetic potential. We are carrying out one of the early efforts to collectively identify novel pathways for sustainable production of natural products from terrestrial Group V cyanobacteria. Figure 1 (bottom) shows the logical sequence of our investigations. Genome sequences collected by our group is routinely mined for unraveling the metabolic diversity of Terrestrial Group V Cyanobacteria through bioinformatics.

Three aims that help us realize the overall goal are to:

  • Clone and heterologously express novel classes of enzymes.
  • Functionally and mechanistically characterize key steps of the biosynthetic pathway.
  • Apply chemoenzymatic steps to combinatorially biosynthesize novel biosynthetic products.


Biosensors for Catalysis and Detection


New genomes require novel ways to reliably identify protein function. Therefore new biochip forming strategies are urgently needed. One of the seminal discoveries our laboratory pursues is toward designing small molecule-engineered protein biochips.  We have developed a new class of electrophiles named smSNAREs that help capture GST or its fusion proteins with remarkable selectivity and ease. Figure 2 shows the details of this strategy.

Suitably modified/tagged proteins are anchored to solid surfaces to result in uniform and reliable orientation. Newly identified biosynthesis enzymes from genomes of microbial organisms become ideal targets to employ this technology to help create enzymatic assays with resource-economy. Recent results from our laboratory reveal that ubiquitous enzymes such as Glutatione S-Transferases can be quite useful to catalyze the immobilization of small-molecules to glass surfaces.

Recently, our work on GST-catalyzed Single Step Protein Immobilization is featured in Bioconjugate Chemistry and The Journal of Organic Chemistry.

Figure 2. A – A SNARE surface probe captures SjGST. B – Fluorescence image of immobilized SjGST. C – Plot consisting of signal intensities for fluorescence image of immobilized SjGST (ImageJ was used for quantification). D – Control experiments comparing SNARE probe surface to epoxy surfaces. E – AFM image and estimation of surface morphology for immobilized SjGST. Click the image for a larger version.




Selected Recent Publications

  • Viswanathan, R.; Labadie, G. R.; Poulter, C. D. "Regioselective Covalent Immobilization of Catalytically Active Glutathione S-Transferase on Glass Slides" Bioconjugate Chem., 2013, 24, 571-577. [Link]
  • Voelker, A. E. and Viswanathan, R. "Self-Catalyzed Immobilization of GST-Fusion Proteins for Genome-Encoded Biochips", Bioconjugate Chem., Article ASAP. DOI: 10.1021/bc400128g
  • Voelker, A. E. and Viswanathan, R. "Synthesis of a Suite of Bioorthogonal GST Substrates and Their Enzymatic Incorporation for Protein Immobilization", Journal of Organic Chemistry Just Accepted Manuscript. [Link]
  • Ignatenko, V. A.; Deligonul, N.; Viswanathan, R. "Branch-Selective Synthesis of Oxindole and Indene Scaffolds: Transition Metal-Controlled Intramolecular Aryl Amidation Leading to C3 Reverse-Prenylated Oxindoles", Org. Lett., 2010, 12(16), 3594–3597. [Link]
  • Ignatenko, V. A.; Zhang, P.; and Viswanathan, R. "Step-Economic Synthesis of (±)-Debromoflustramine A Using Indole C3-Activation Strategy" Tetrahedron Lett. 2011, 52, 1269-1272. [Link]