Nanoparticles for drug delivery of chemotherapeutic agents have emerged as potential next generation treatments for many cancers, offering the potential of improving chemotherapeutic efficacy while drastically minimizing off target toxicity and side effects. However, several physiological barriers limit their bioavailability and efficacy. While solutions to overcome some of these have been proposed, the reliable design and production of efficacious nanoparticles remains a significant challenge. Using advances in the fields of synthetic biology, metabolic engineering and enzyme engineering, we have developed initial tools for the rapid design and scalable biosynthesis of custom, specific and genetically programmable nanoparticles for advanced drug delivery. Specifically, we have engineered the biosynthesis of site specifically lipidated peptides for the programmable self-assembly of nanoparticles. The approach has included engineering the fatty acid biosynthesis pathway to produce specific chain length fatty acids, which can be attached site specifically to any peptide of interest via engineered fatty acid transferases such as the N-myristoyl transferases (NMT), with alterations in substrate specificity. This general approach allows for the elucidation of molecular design principles of the engineering of advanced materials composed of conjugated peptides.

In vivo synthesis of nanoparticles through evolved peptide lipidation

251st National Meeting (2016)

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