While other biochemists unravel the mysteries of natural enzymes, Christin Choma, associate professor of biochemistry, is attempting to design completely synthetic ones from scratch. The process, called de novo protein design, should one day allow Choma and other protein designers to construct catalytic proteins with unique characteristics, in addition to controlling the size, shape, solubility, and activity of the protein catalyst.

Building designer enzymes — those with a purpose specifically tailored to their environment or function — has future industrial applications for bioremediation of land and water contaminated by the mining, petroleum, and ore processing industries, as well as for pharmaceutical and fine chemical production, Choma says.

Scientists have understanding of how natural proteins fold and function, but don’t have control over how, when, or why they fold. In de novo enzyme design, a protein sequence is generated and directed to fold into a synthetic and predicted 3-D structure that exhibits defined catalytic capabilities. The synthetic sequence bears no intentional resemblance to the sequence of a natural protein. Since designed proteins are not constrained by the same limitations as natural proteins, unnatural amino acids and cofactors can be readily incorporated.

“This should allow us to eventually design enzymes for specific ‘unnatural’ tasks, such as cleaning the Hudson River of PCBs, or ‘eating’ oil that has leached into the soil around an abandoned industrial facility,” says Choma.

“Presently, we are designing small proteins that can selectively oxidize a variety of compounds,” she says. “The goal is to lay the foundation so that the design of purpose-specific enzymes will become a reality within the next 10 years. The implications for the chemical, biotechnology, and pharmaceutical industries are enormous.”

As published in Rensselaer’s Campus.News, June 3, 2002

Published June 3, 2002