Biochemistry

Biochemist coaxes enzymes to make new biological drugs

Believe it or not, a young man once got turned on to an exciting career by watching paint dry. As a student at Cleveland State in the mid-70s, Romas Kazlauskas worked for a company that made the lead compounds that catalyzed the drying process, speeding it up. The experience sparked a lifelong interest in catalysts and how they can be harnessed for new jobs. Now an associate professor of biochemistry, molecular biology, and biophysics, Kazlauskas is a chemical architect, building both new drugs and new drug-synthesizing enzymes. His goal is more efficient and greener (less polluting) routes to the next generation of drugs.

Romas Kazlauskas, new faculty member in the Department of Biochemistry, Molecular Biology, and Biophysics, induces the evolution of enzymes to find new medicines.

"We're trying to evolve enzymes to synthesize new drugs, and we're also evolving small molecules and screening them for their potential as drug precursors," Kazlauskas says.

Raised in Cleveland by Lithuanian immigrant parents, Kazlauskas left his home town for graduate school at MIT in Cambridge, Mass. After receiving his Ph.D. in 1982, he moved a stone throw up the Charles River to Harvard for a three-year postdoctoral position.

"It was an exciting place to be," he recalls. 'You could feel the energy everywhere.'

Some of that energy came from series of developments in chemistry. Kazlauskas and his contemporaries discovered how to tap the powers of natural enzymes for everything from cleaning fabrics to making new drugs. He took that knowledge to a job at General Electric in Schenectady, N.Y., where he studied the biodegradation of PCBs. After three years at G.E., he joined the faculty of McGill University in Montreal, where he spent the next 15 years.

A big hurdle in the manufacture of drugs is getting around the fact that many drugs are like gloves they come in left- and right-handed forms. Usually, only one form is useful. The trick is to make sure that in each chain of chemical reactions leading to synthesis of a drug, only chemicals of the correct 'handedness' are formed.

To that end, Kazlauskas is mutating genes for enzymes that catalyze such reactions, aiming to produce new enzymes that will lead to new drugs without producing byproducts of the wrong handedness. He also uses traditional chemical means to generate novel molecules, which he then tests for drug-like activity. In short, he is advancing the search for new drugs by evolving both new enzymes and new molecules with potential as drugs.

Also, some of his new enzymes may find uses in industry as replacements for chemical processes that produce environmental pollutants.

A globetrotter, Kazlauskas collaborates with scientists in Montreal and Sweden. Four years ago, he visited his ancestral country for the first time when he attended a conference in Vilnius, Lithuania. As a fluent speaker of Lithuanian, he got around just fine.

Back home, Kazlauskas keeps physically active by running the three miles from Gortner Lab to his home, which he shares with his wife and three children.

Deane Morrison