Chinese Scientists Develop Better Biotech Enzymes

A Chinese research team has demonstrated an essential principle in altering the activity of enzymes by way of protein engineering.

The research team was led by Prof. Kam-bo Wong of the Center for Protein Science and Crystallography, School of Life Sciences at the Chinese University of Hong Kong SAR (China). The study's findings provide promising insights into the future design of biotechnologically important enzymes, and it will be published in the March 21, 2011, issue of the online, open access journal PLoS Biology.

Proteins from thermophiles, organisms that live in high temperatures, are more resistant to heat denaturation than those from mesophiles, organisms that live in moderate temperatures. In nature, enzymes from microbes that thrive in extremely hot habitats like hydrothermal vents can remain stable even at 100 °C. These thermophilic enzymes are useful for the biotech industry because of their superior stability.

An intriguing problem is that thermophilic enzymes are less active than their mesophilic homologs despite having similar structures. "It is like two cars having similar engines but one runs 10 times faster than the other. If thermophilic enzymes can be made more active without compromising their stability, it will be of great commercial value to the biotech industry,” explained Prof. Wong.

The research team employed protein-engineering techniques to investigate why thermophilic enzymes are less active. They found that the thermophilic enzyme acylphosphatase has a unique property in that its active site is rigidified by a salt-bridge. Thermophilic enzymes tend to have more stabilizing interactions such as salt-bridges. By removing this salt-bridge, the scientists converted thermophilic properties of acylphosphatase to mesophilic-like properties. Similarly, a mesophilic acylphosphatase from human was engineered to become thermophilic-like by introducing the salt-bridge.

The investigators concluded that the rigidifying salt-bridge increases the activity of enzymes at high temperatures, but at the same time reduces the activity at low temperatures. It is hoped that data gleaned from Prof. Wong's study will lead to the improvement of enzymes in the biotech industry.

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