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An enzyme is like a Symphony

awarded For the invention of "directed Evolution", i.e. the biological optimization of proteins – was Frances Arnold (62) from the California Institute of Technology this year's Nobel prize for chemistry. Two years previously, she had received over a Million francs doped Millennium Technology Prize. Researchers around the world rely on the Arnold since 1993 developed methods to micro-organisms convert small organic witness.

"Hardly a method, the invented people is not nearly so powerful."

Frances Arnold, you have studied mechanical engineering and aeronautical engineering and in chemistry a PhD, but work with biological molecules. What an engineer is irritating to the biology?
I wanted to develop about 25 years ago a more effective, more environmentally-friendly chemistry, and I quickly found that the nature is second to none in this relationship. You take the catalysts in every biological cell is active, the enzymes. Provide selective products, which needs the cell, with high yield and minimal waste. Hardly a method, the invented people is not nearly as powerful. I'm sorry for the chemist, but that's how it is. This molecular super-machines, the enzymes, I wanted to make use of it.

How did you approach this?
I relied on the principles of Evolution, the best designer of all time. She has optimized over billions of years the enzymes. And she's still doing it. So it was thought, for decades, the herbicide atrazine for non-biodegradable. For So long, until it reached the first microbes, to remove the chlorine atom from the herbicide and use the Rest as a valuable source of nitrogen.

There are a myriad of different enzymes. How do you find out which will provide you with the Training to start?
This is only possible with a lot of experience. If you want to breed a racehorse, do you start with a donkey. I see the skills involved in an enzyme, even if it takes a couple of mutations, until you emerge.

do you Have any favorite horses?
Yes, the Cytochrome.

Video – Nobel prize in chemistry for the directed Evolution of enzymes

The proteins present in the respiratory chain of animal cells, but also in photosynthesis.
There are true all-rounders. Thanks to its heme group with an iron atom in the center, you can transfer electrons, oxygen atoms move, and speed up chemical reactions. We have cabinets at the California Institute of Technology, thousands of different Cytochromes digital in our databases and physically in our freezer.

How to train Cytochromes?
An example: We wanted to bring these enzymes, chemical Compounds of silicon and carbon. These are substances that no living organisms, but in our everyday lives, we use them constantly, such as silicone gaskets, glue or toothpaste. To produce you need, chemist, high temperatures and expensive catalysts – enzymes, it was previously impossible. In our databases we found a promising cytochrome from a bacterium that lives in hot, salty pools in Iceland.

And you what did?
We identified the amino acids that Make sassen, could be for the desired reaction is important, and to be replaced by others. Then we examined their chemical activity, and more made with those who delivered the best results. As in Darwin's theory of evolution, we therefore made use of Mutation and selection, only. This is what we call directed Evolution. In this specific case, we needed only three mutations to develop a drug that produces the desired Compounds.

If you install it then in microbes, produces the enzyme chemicals for the industry?
Yes, and many times more efficient than current chemical catalysts, at room temperature, in water, without any solvents, wastes, and with a simple iron instead of expensive precious metals – all we need to do is to feed the bacteria with a little sugar.

"enzymes in detergents today are genetically modified."

Is used technically?
For the optimization of enzymes, directed Evolution is currently the method of choice. As an important medicine for type 2 Diabetes is made, in the meantime, with enzymes, Compared with the previous, purely chemical process, you need to have no toxic heavy metals, and waste solvents could be reduced by 60 percent. Enzymes in Laundry detergents today are genetically modified.

you also produce such products?
At the University, we conduct basic research, but we have established from our Team out of the Start-up company, about the company Gevo, the use of enzymes Isobutanol produced from biomass. That is a raw material for plastics, and jet fuel. Especially exciting I think our new company Provivi. Here with the help of enzymes produced natural pheromones of insects – at a significantly lower cost than was previously possible.

Why do you need these fragrances?
If you are sprayed over corn fields, the corn borer to each other. The Moths can't reproduce, and there is no voracious caterpillars. The plant protection without insecticides.

"people have created breeds for a variety of dog that would not exist without us."

you bring bacteria to produce things that do not exist in any biological cell.
Properly, and that's what we do, not only out of academic curiosity. Our Holy Grail is currently carbon-fluorine molecules. These are for the pharmaceutical industry is very important – from the antibiotic over the cholesterol-lowering drug to sleep. However, they are difficult to manufacture and only with a high environmental impact. We think that we can also create the optimized enzymes.

we Are designing for in the future, the life completely new?
actually, we do that for thousands of years. So people have created in only 500 dog generations, a variety of breeds – from poodles to St. Bernards – that would not exist without us. Of today's cereal and fruit - not to mention places. But of course, we are now much more targeted to the genome: can We invent the Computer, any combination of DNA letters that you Mail to a specialized company to send, and a few days later, we have a box of the DNA molecules in the letter. We can inject then in biological cells and look at what the bacterium, Alga or a yeast begins.

And before that, it was all simulated on the Computer?
This is the crux of the matter, because that doesn't work. You take a drug, my favorite of the enzyme with 500 amino acids. If you wanted to at any point in all of the 20 existing amino acids, would result in the 20 high 500 possible mutations, an unimaginable number with 650 zeros. Not to add to that: How a Mutation affects the spatial folding of the Protein, we do not really – and how its function changes. But the beauty of directed Evolution is: We don't have to understand everything, we just need to use Mutation and selection in an intelligent way. How wrong we can be, we have just seen the bacterium from the Island ponds.

"A functioning enzyme can only invent Evolution."

to what Extent?
With a computer simulation, we have discovered that the cytochrome of this bacterium has no free active center, and the molecule is probably discarded. However, with only three of the mutations we had success. And even more: Often the best are the mutations at sites in the enzyme, which are spatially far from where we would have expected mutations.

This means that researchers are not designing for the foreseeable future on the Computer and completely new enzymes?
For me, it is an enzyme, such as a Symphony by Beethoven. Its amino acids and the letters of the DNA, which determine the respective amino acid, correspond to the musical notes. We can read the notes and change, we can cut out the individual chords and paste them, but we are still far from able to compose a perfect Symphony, that is to say to invent a functioning enzyme. The only the Evolution.

(editing Tamedia)

Created: 10.12.2018, 13:44 PM

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