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Shifting evolution into reverse promises cheaper, greener way to make new drugs
Date:3/23/2014

This alternative approach to creating artificial organic molecules, called bioretrosynthesis, was first proposed four years ago by Brian Bachmann, associate professor of chemistry at Vanderbilt University. Now Bachmann and a team of collaborators report that they have succeeded in using the method to produce the HIV drug didanosine.

The proof of concept experiment is described in a paper published online March 23 by the journal Nature Chemical Biology.

"These days synthetic chemists can make almost any molecule imaginable in an academic laboratory setting," said Bachmann. "But they can't always make them cheaply or in large quantities. Using bioretrosynthesis, it is theoretically possible to make almost any organic molecule out of simple sugars."

Putting natural selection to use in this novel fashion has another potential advantage. "We really need a green alternative to the traditional approach to making chemicals. Bioretrosynthesis offers a method to develop environmentally friendly manufacturing processes because it relies on enzymes the biological catalysts that make life possible instead of the high temperatures and pressures, toxic metals, strong acids and bases frequently required by synthetic chemistry," he said.

Normally, both evolution and synthetic chemistry proceed from the simple to the complex. Small molecules are combined and modified to make larger and more complex molecules that perform specific functions. Bioretrosynthesis works in the opposite direction. It starts with the final, desired product and then uses natural selection to produce a series of specialized enzymes that can make the final product out of a chain of chemical reactions that begin with simple, commonly available compounds.

Bachmann got the idea of applying natural selection in reverse from the retro-evolution hypothesis proposed in 1945 by the late Caltech geneticist Norman Horowitz. Horowitz envisioned an early stage in
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Contact: David Salisbury
david.salisbury@vanderbilt.edu
615-343-6803
Vanderbilt University
Source:Eurekalert

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