Principal Investigator T Hatton
Co-investigators Bernhardt Trout , Stephen Buchwald , Kenneth Smith , Gregory Stephanopoulos
Project Website http://web.mit.edu/sma/research/cpe/index.htm
The Flagship project, Molecular Engineering of Bio/Chemical Pathways & Process Science for the Pharmaceutical Industry, addresses an area of industrial practice that is important for the future of Singapore's industry, specifically the pharmaceutical industry. The Flagship project consist of 3 thrusts, metabolic engineering, chemical catalysis and downstream processing, which complement one another with the expectations of great results for the development of pharmaceuticals for Singapore. Specifically, the research program will focus on developing new technologies and cutting edge methods for the production, synthesis, separation, and formulation of pharmaceuticals, with a focus on chemical pharmaceuticals.
The first thrust focuses on metabolic engineering, where molecular biotechnology is used to engineer pathways for the synthesis of chiral compounds and other Active Pharmaceutical Ingredients (APIs). The objectives for this program are to discover new clones and techniques for bioconversion; to develop tools to enable rapid, modularized approaches to recombinant biocatalyst construction; to engineer processes with enhanced bioconversion efficiencies for chiral compounds with high enantiometric excess; to enhance the efficiency of synthesis of valuable pharmaceuticals, such as Artemisinin (an anti-malaria drug), and to combine biocatalysis in vitro with co-factor regeneration, thus, solving important current technological problems.
A second focus area of the flagship project is chemical catalysis, where we target to efficiently synthesize chiral compounds by designing catalysts at the molecular-nanometer scale. The objectives for this project involve the synthesis of novel homogeneous organopalladium complexes for carbonylation reactions at low carbon monoxide pressures and moderate temperatures, which will have a major impact on the synthesis of esters and amides in the pharmaceuticals industry; the development of new chiral indium complexes that are water-stable and oxygen-tolerant for catalyzing various organic transformations, leading to not only environmentally friendly processes, but also simplified synthetic strategies; and the design and synthesis of nanoporous supports to immobilize chiral organometallic complexes, facilitating the recovery and reuse of the proposed organometallic ligands and leading to more efficient synthesis of chiral pharmaceuticals via continuous reactor schemes.
Downstream processing for the development of novel separation and purification concepts is the third pillar of the flagship project, whereby molecular engineering is used to achieve isolation, purification and formulation of proteins and small molecular drugs. In this part of the flagship project, we will develop new, commercially viable methods for separations, study interactions among biological molecules, and engineer novel formulations for biotherapeutics. This work has the potential to enhance significantly industrial efficiency via new processing methods and new analytical approaches. Another aim is the development of new means of delivery of biopharmaceuticals.
Seven Inter-University Research (IUR) projects have been assembled. The IUPs are compatible with the Flagship theme, while not having direct overlap.