Laboratory for Bioinformatics and Metabolic Engineering

The Bioinformatics & Metabolic Engineering Laboratory at focuses on diverse challenges in the fields of Metabolic Engineering and Bioinformatics. Research is focused on Metabolic Engineering - the improvement of cellular properties, using modern genetic tools. This field encompasses two important components: (1) The modification of biochemical pathways inside cells, and (2) The rigorous evaluation of the resulting cellular phenotypes.

Most recent research has been focused on the following topics:
(*) Metabolic Engineering of E.Coli for the production of biochemicals
(*) Inverse Metabolic Engineering
(*) gTME
(*) Flux Determination
(*) Hepatocyte Physiology
(*) Metabolomics
(*) Rational Drug Design
(*) Systems Biology

To accomplish these goals we make use of a diverse array of scientific tools and methods, many of which have also become areas of research for the group:

(*) Bioinformatics and Systems Biology -- The group was one of the first to realize the importance of computational tools for handling the large volume of data generated by microarrays and other technologies.
(*) Methods for intracellular flux determination - Fluxes are determined by material balancing, NMR fine spectra analysis and GC-MS measurements.
(*) DNA microarrays -- We have developed full genome microarrays for Synechocystis Sp., and partial microarrays for C. glutamicum, E. coli, and the mouse genomes.
(*) Bioreaction network analysis

Natural Products -- The isoprenoid “superfamily” has generated considerable interest among the scientific community in recent years owing to the demonstrated therapeutic potential of several of its 40,000-odd members. Prominent among these are menthol, artemisinin, lycopene and taxol. The high specificity and efficacy of these molecules have caught the attention of several large pharmaceutical corporations, and many in the pharmaceutical industry now opine that the next wave of blockbuster pharmaceuticals could possibly originate from this superfamily. Consequently, isoprenoid production has emerged as a highly lucrative enterprise and this has prompted several research groups across the globe to take up this challenge. Of the variety of approaches to have been proposed over the years, de novo chemical synthesis, extraction from plant matter and production in microbial hosts are perhaps the best known. Most of the therapeutically active isoprenoids possess heavily substituted chemical structures that are often cyclized with multiple chiral centres – a level of structural complexity that precludes synthesizing these chemicals in vitro. Extracting these compounds from plant matter is equally encumbered, and both these approaches are abysmally low yielding. On the other hand, producing these compounds in microbial hosts such as Escherichia coli offers several advantages, including environmental benignity and use of inexpensive sugar-based carbon inputs. A synergism of bioprocess optimization and metabolic engineering promises high titre production of these therapeutic molecules and offers a commercially viable alternative to the production of bioactive plant-derived chemicals.

Isoprenoid biosynthesis in microbial hosts ranks among the group’s major research initiatives and current work in the laboratory focuses on the production of taxol and geraniol in E. coli and S. cerevisiae.