Teaching cells to create and harness non-standard amino acids
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Proteins are incredible polymeric nano-machines and the molecular workhorses of cells. Despite their diversity of structure and function, their abilities are limited by the chemistry of the twenty standard amino acids used for protein synthesis. We will teach cells to make and integrate amino acids that can respond to a variety of stimuli, initiate various processes, and form chemical bonds with biologically orthogonal functional groups. By doing so, we will enable precise control of proteins and polypeptide biomaterials without perturbing their structure.
Relevant papers: De novo biosynthesis of para-nitro-L-phenylalanine in Escherichia coli |
Advancing safeguards that control proliferation of engineered microbes
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Living cells are capable of targeting regions of the body or influencing other organisms in the environment in unique ways. Synthetic biologists have created many tools to make engineered organisms more powerful and more useful in settings outside of traditional reactors, such as when administered to patients or released in the environment. To responsibly harness these new opportunities for engineered microbes, we need to better develop and characterize techniques for intrinsic biocontainment. We are especially interested in synthetic auxotrophy, where an organism is engineered to depend on a synthetic nutrient for growth.
Relevant papers: Synthetic auxotrophy remains stable after continuous evolution and in coculture with mammalian cells Designing efficient genetic code expansion in Bacillus subtilis to gain biological insights Engineering posttranslational proofreading to discriminate nonstandard amino acids |
Upgrading lignin and plastics using biocatalysis for polymer synthesis
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The bulk of materials that we use in our daily lives are currently sourced from petroleum. Meanwhile, the majority of plastic that we use ends up in landfills, and the lignin that is leftover from products in forestry or agriculture is burned. These carbon-rich materials that are often discarded as waste can be broken down, but research is needed to identify efficient routes and end uses that justify the processing cost. At Delaware, we participate in two interdisciplinary projects where we collaborate with prominent researchers in catalysis and polymer science to create higher value materials from lignin and plastic. We use biocatalysis to selectively introduce chemical functional groups that give these materials valuable properties.
Relevant papers: Reductive Enzyme Cascades for Valorization of PET Deconstruction Products Combinatorial gene inactivation of aldehyde dehydrogenases mitigates aldehyde oxidation catalyzed by resting cells of E. coli RARE strains |
