June 25, 2004 | David F. Coppedge

Biochemists Mutate Protein, Make a Catalyst

“Enzymes are among the most proficient catalysts known,” wrote three Duke University scientists, “and they catalyze a wide variety of reactions in aqueous solutions under ambient conditions with exquisite selectivity and stereospecificity.”  The team set out to rationally design their own enzyme.  Their work is reported in the June 25 issue of Science.1  Building on a non-enzymatic ribose-binding protein, they introduced 18 to 22 mutations at specific points, imitating the active site of triose phosphate isomerase (TIM).  They succeeded in getting a million-fold increase in catalytic activity, and showed their NovoTim invention to be biologically active in E. coli bacteria.  To them, not only does this demonstrate scientists’ ability to understand and imitate “naturally evolved” enzymes, but the “introduction of TIM activity into RBP is therefore equivalent to convergent evolution by computational design.”  Their enzyme was less thermally stable than the wild type, however, and the reaction rate was 220 times lower.


1Dwyer, Looger and Hellinga, “Computational Design of a Biologically Active Enzyme,” Science, Vol 304, Issue 5679, 1967-1971, 25 June 2004, [DOI: 10.1126/science.1098432].

We hate to have to award these clever inventors the Stupid Evolution Quote of the Week prize, but listen to what they said.  They just called themselves blind, deaf and dumb.  Here they used intelligence, ingenuity, know-how, knowledge, and supervision to design a working enzyme, then said it was equivalent to “convergent evolution,” a blind, purposeless process that has none of those things.  Their work has nothing to do with evolution, convergent, divergent, invergent, subvergent or otherwise.  It was an exercise in reverse engineering.  By emphasizing the specificity of contact points in a simple enzyme that leads to efficient catalysis, their work underscores the necessity of rational design.  How come Charlie keeps getting credit for intelligent design work?  Unfair.

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Categories: Cell Biology, Dumb Ideas

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