Understanding enzyme evolution paves the way for 'green' chemistry


Date:
August 19, 2021
Source:
University of Bristol
Summary:
Researchers have shown how laboratory evolution can give rise
to highly efficient enzymes for new-to-nature reactions, opening
the door for novel and more environmentally friendly ways to make
drugs and other chemicals.



FULL STORY ========================================================================== Researchers at the University of Bristol have shown how laboratory
evolution can give rise to highly efficient enzymes for new-to-nature reactions, opening the door for novel and more environmentally friendly
ways to make drugs and other chemicals.


========================================================================== Scientists have previously designed protein catalysts from scratch using computers, but these are much less capable than natural enzymes. To
improve their performance, a technique called laboratory evolution can be
used, which American chemical engineer Frances Arnold pioneered and for
which she received the Nobel Prize in 2018. Directed evolution imitates
natural selection, allowing scientists to use the power of biology to
improve the ability of proteins to carry out tasks such as catalysing
a specific chemical reaction.

But although the research team had recently used laboratory evolution
to improve a designed enzyme by more than 1,000 fold, it was unknown
how evolution boosts its activity. Until now.

Lead author Professor Adrian Mulholland of Bristol's School of Chemistry
said: "Evolution can make catalysts much more active. The thing is,
evolution works in mysterious ways: for example, mutations that apparently improve catalysis often involve changes in amino acids far from the
active site where the reaction happens." "We wanted to understand how evolution can transform inefficient designer biocatalysts into highly
active enzymes.," the first author of the study, Dr Adrian Bunzel, said.

To do so, the international research team from Bristol, the ETH
Zurich and the University of Waikato (NZ) turned to molecular computer simulations. "These show that evolution changes the way the protein
moves -- its dynamics. Put simply, evolution 'tunes' the flexibility of
the whole protein," he added.

The team also identified the network of amino acids in the protein
responsible for this 'tuning'. These networks involve parts of the
protein that are changed by evolution.

Dr Bunzel said: "After evolution, the whole protein seems to work together
to accelerate the reaction. This is important because when we design
enzymes, we often focus only on the active site only, and forget about
the rest of the protein." Prof Mulholland added: "This sort of analysis
could help to design more effective 'de novo' enzymes, for reactions
that previously we could not target." The research, published in Nature Chemistry, reveals how evolution makes designer enzymes more powerful,
paving the way to tailor-made catalysts for green chemistry.

The researchers will now use their findings to help design new protein catalysts.

========================================================================== Story Source: Materials provided by University_of_Bristol. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. H. Adrian Bunzel, J. L. Ross Anderson, Donald Hilvert, Vickery
L. Arcus,
Marc W. van der Kamp, Adrian J. Mulholland. Evolution of dynamical
networks enhances catalysis in a designer enzyme. Nature Chemistry,
2021; DOI: 10.1038/s41557-021-00763-6 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210819113054.htm

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