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Overview

The exploration and development of enzymes for a wide range of polymer forming and modifying reactions is under study. By using enzyme-catalysis we are able to reduce reaction temperatures and provide mild-reaction conditions. This enables the use of chemically sensitive building blocks that would not otherwise survive the harsh conditions that occur when chemical catalysts are used. Examples of in-vitro enzyme-catalyzed polymerizations/modifications include lactone ring-opening, condensation polymerizations, oligopeptide synthesis, vinyl free radical and oxidative crosslinking. This work seeks to create functional polymers by exploiting enzyme regioselectivity, control chain stereochemistry, obtain products of narrow polydispersity, and design polymers that would otherwise not be possible or very difficult to prepare by traditional chemical methods. Polymerizations are studied by using classical techniques to determine kinetic parameters and mechanism.

Our laboratory is also investigating novel ways that enzymes can be used to modify polymers. Examples are enzyme-catalyzed selective covalent attachment of biologically active molecules to fibers and nanoparticles. Enzymes are also being studied that function to remove layers of molecules from surfaces of fibers and other processed materials. This function of enzymes enables bio-polishing that is surface-cleaning.

Altering a polypeptide's function by changing its sequence allows natural proteins to be converted into useful molecular tools. For example, protein catalysts in microbes or plants were optimized through millions of years to function within their natural environment, not the environment they will encounter during a commercial process. We are working with DNA2.0 to refine and test computational enzyme engineering tools. Our goal is to use these methods to redesign enzymes for monomer and polymer enzyme-catalyzed biotransformations. Amino acid changes likely to modify (but not destroy) enzyme activity are selected computationally by considering phylogenetic and structural information. These changes are incorporated into <100 variants that are synthesized, expressed and tested. Each variant set contains a wide range of activities towards the target substrates.

Enzyme families studied in the group for biocatalytic transformations

• Lipases
• Proteases
• Esterases
• Cutinases
• Glycosidases
• Peroxidases
• P450

Polymer Families under study:

• Bioresorbable polyesters, polycarbonates and polyurethanes
• Polymers from fatty acids
• Oligopeptides
• Microbial Polyesters
• Microbial Peptides
• Microbial glycolipids
• Microbial polysaccharides

Medical research targets of the Richard A. Gross research group include:

Bioresorbable polymers for drug delivery and use for structural/biologically active materials during wound-healing. Water-soluble polymers for drug targeting. Functional oligomers for drug delivery by in-situ crosslinking. Functional micro- and nano-particle drug delivery systems. Structure-activity relationships of microbial glycolipids. This work has focused on sophorolipids and structural analogs. Their activity for immunoregulation, antiviral and antimicrobial properties is under study. Mild crosslinking reactions that create hydrogels for cell entrapment, growth and differentiation.