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Tom Wright
Tom Wright

It has been stated so many times on the internet that it must be true – if the 20th century was the century of physics, the 21st century will be The Age of Biology.
The popular science literature is so filled with whole genomes, synthetic cells and glow-in-the-dark kittens it’s hard not to doubt the proposition. So, for arguments sake, let’s accept it as true. Where does that leave chemistry, the ‘central science’, wedged somewhere between physics and biology, crucial to modern life yet so often taken for granted, feared or plain forgotten?

Specifically, what does The Age of Biology imply for those of us working our arses off to create a greener chemistry better suited for the grand challenge of our century- providing increased standards of living without trashing the planet in the process? Over my next few posts, I intend to explore this question.

There are two ways biology can influence green chemistry

as a template/model and as a tool. Natural ecologies offer the only example we have of a no-waste, circular economy powered by sunlight – exactly the limit horizon of what we should be aiming for in our human industries, as I will expand on in a later post.

Let’s talk tools:

As a nested system, the biological world offers solutions to chemists at various scales –at the level of proteins (enzymes), pathways, whole cells and ecologies. However, it is enzymes that do the actual business of making and breaking chemical bonds, making it no surprise that enzymes have captured chemists’ imaginations for over a century. Biocatalysis is the science of harnessing enzymes for the creation of new medicines, materials and fuels. To give an idea of the growing influence of biocatalysis in the chemical industry, the recently announced CHEM21 project brings together six pharmaceutical companies, five smaller enterprises and 13 universities in a four-year, €26.4 million partnership strongly focussed on the development of biocatalysis and synthetic biology techniques for pharmaceutical synthesis.

 

This is exciting stuff because…

from a green perspective, enzymes are the ideal catalysts.

 

The key reason is the high selectivity of enzyme catalysts for specific transformation of individual functional groups (chemoselectivity) and geometries (enantioselectivity) in a target molecule. This results in reduced by-product formation, increasing yield and simplifying isolation of the desired product. Using an inherently biodegradable protein to replace toxic metal catalysts further simplifies purification and clean-up. Enzymatic processes also work at ambient temperatures, pressures and in water, saving energy and making for safer chemistry.

All of these features make enzymes attractive, especially for the preparation of fine-chemicals and pharmaceuticals, which tend to be particularly wasteful. As a recent illustration of the power of biocatalysis, the replacement of a rhodium-catalysed asymmetric hydrogenation step with enzymatic catalysis in the Merck synthesis of the anti-diabetic sitagliptin increased yields by 10-13% while reducing total waste by 19%, netting a Science paper in the process!

The sitagliptin work represents the growing power of state-of-the-art molecular biology techniques. Advances in gene synthesis (chemistry!), directed evolution (see diagram) and high-throughput screening have allowed protein engineering to accomplish the equivalent of transforming millions of years of evolutionary changes into the lab work of months.

On the horizon is the computational design of enzymes, work pioneered by David Baker’s group, who have designed enzymes with atomic-level accuracy to  catalyse the Diels-Alder reaction, one of the most ubiquitous and powerful reactions in organic chemistry, and the Kemp elimination, reactions for which there are no known natural enzymes. The Baker group have even used the computer game Foldit to enlist players around the world in a crowdsourced effort to improve these enzymes – improving the catalytic activity of the Diels-Alderase 18 times. If you’re looking for an alternative to Angry Birds, I guess you could do worse.

 

Further reading:

Review of biocatalysis for green chemistry: 10.1039/B716045C

Chem21: http://www.chem21.eu/

Sitagliptin: 10.1126/science.1188934

Diels-Alderase: 10.1126/science.1190239

10.1038/nbt.2109

Foldit: Fold.it

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