Romas Kazlauskas

Our laboratory engineers nature's most sophisticated chemical tools — enzymes — to solve pressing global challenges. We've discovered that creating better enzymes requires redesigning entire protein neighborhoods, not just the obvious active sites. By systematically modifying dozens of precisely chosen amino acid building blocks, we can transform one type of enzyme into another, teaching old proteins entirely new functions.

This deep understanding of protein networks allows us to develop enzymes that break down stubborn environmental pollutants, including PFAS "forever chemicals" that contaminate water supplies worldwide. Our work bridges millions of years of evolutionary design with modern engineering principles, creating solutions for environmental cleanup, sustainable manufacturing, and therapeutic development.

Our laboratory advances enzyme engineering through systematic protein redesign, focusing on the critical role of second-shell residues in catalytic function. We have demonstrated that successful enzyme conversion requires extensive remodeling of structural neighborhoods extending 6-14 Å beyond the active site, challenging traditional active site-focused approaches to protein design.

Our research elucidates the allosteric networks that govern catalytic efficiency, revealing how distant residues orchestrate active site geometry and dynamics through long-range effects. This mechanistic understanding enables us to engineer enzymes for challenging applications, including the biodegradation of recalcitrant environmental contaminants such as PFAS compounds, which resist conventional degradation pathways.

By integrating structural biology, computational design, and systematic mutagenesis, we develop predictive frameworks for enzyme engineering that bridge evolutionary principles with rational design strategies. Our work establishes new paradigms for protein engineering, providing both fundamental insights into enzyme function and practical solutions for environmental remediation, sustainable catalysis, and biotechnological applications.

Biocatalysis uses enzymes for unnatural purposes — synthesis of drugs, chemical intermediates, and biofuels. Using enzymes creates more efficient syntheses that minimize pollution and avoid toxic and non-selective chemical reagents.

Nature's enzymes have evolved to efficiently catalyze biochemical reactions, so they need modification for other applications. Protein engineering makes these modifications. Protein engineering can increase the stability, selectivity, reaction rate, and can even change the normal reaction catalyzes to a different reaction type.

Current protein engineering dramatically improves protein properties. Engineered proteins can be millions of times better for their new application as compared to natural proteins. In one case, researchers replaced 15% of the amino acids in the protein. This is equivalent to engineering a mouse into a human, since mouse proteins typically differ from human proteins by 15%.

Examples of current research:

• The biggest barrier to converting inexpensive biomass to fuels is efficiently extracting the sugars from biomass. The lignin component of biomass is like the glue in fiberglass that protects the sugar fibers. Peracetic acid is a strong oxidant that can break down lignin, but it is too expensive to manufacture. We are engineering enzymes to efficiently produce peracetic acid. Besides biofuel manufacture, enzyme-generated peracetic acid may be a green oxidizing reagent for organic synthesis and a water disinfectant for developing countries.
• As biomass replaces petroleum as the feedstock for fuels, it should also be the feedstock for chemicals. One promising source is lignin, a waste product from cellulosic biofuels manufacturing. To use lignin fragments, we are inventing new biochemical pathways, even new biochemical reactions to convert them into starting materials for chemical synthesis.
• Current protein engineering starts with enzymes from nature, but ancestral enzymes may be a better starting point. Current specialist enzymes evolved from ancestral stem-cell-like enzymes that catalyzed many related reactions; they were generalists. Using reconstructed ancestral enzymes as the starting point may yield new specialist enzymes more quickly.

Postdoc: Harvard U.
visiting prof.: Stuttgart U. ('95-'96), KTH Stockholm ('02-'03), Seoul Nat'l U. ('09-'13).

What's New

• Protein engineering
• Sustainable chemistry