ME: Combinatorial, in Vitro Manipulation of a Polyketide Synthase Pathway on a Microscale

  • Dordick, Jonathan (PI)

Project Details


The objective of the proposed research is to use in vitro metabolic engineering combined with combinatorial biology and microscale processing to evaluate the functional diversity of a complex metabolic network, namely, polyketide synthesis. The investigators will develop a microscale, microfluidic device for the in vitro combinatorial biosynthesis of complex polyketides. Also, because of the microscale component and the modularity of the polyketide synthesis, the investigators expect to use the principles of multi-step enzymatic networks (e.g., a metabolic pathway) to alter the progress of the pathway and generate unique compounds. The class of polyketides used in this research consists of a small number of polypeptides each containing multiple modules. Each module is responsible for one round of chain extension and post-condensation modifications. The modules will be immobilized into the channels of the microfabricated device, a mutant thioesterase domain will be engineered into each module (necessary for release and transport to the next module), and the products will be transported from one module to the next. This research could enable the synthesis of molecules with new and unusual functions. Also, this research could add to the fundamental understanding of metabolic pathways and microfluidics.

Effective start/end date15/08/0131/07/05


  • National Science Foundation: $371,603.00


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