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Ross

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Festive special: The brewer's tale
23 December 2006
From New Scientist Print Edition.
Andy Coghlan

NEXT time you raise a glass of something alcoholic to your lips, spare a thought for the humble organism that makes it all possible. From the crudest home brew to the most exquisite champagne, the production of almost all alcoholic drinks depends on the single-celled fungus we call brewer's yeast.

Some time in the distant past Saccharomyces cerevisiae, to give it its full name, developed a chemical trick that would transform human societies. Some anthropologists have argued that the desire for alcohol was what persuaded our ancestors to become farmers and so led to the birth of civilisation. Whether that's true of not, alcohol has had a huge influence on our history and our prehistory (see "It's in our genes").

So what made S. cerevisiae such a great brewer in the first place? How come this organism converts just about any sugar-rich solution, from squashed fruit to mashed-up grains, into that intoxicating substance enjoyed by so many of us? Some remarkable genetic detective work has revealed just how and why the yeast acquired its talents - and it's a dark tale of war and sacrifice.

While we take yeast's brewing abilities for granted, they are in fact rather surprising. Most organisms that generate energy from sugars to use oxygen to break the molecules down into water and carbon dioxide. The energy this releases is stored in the form of adenosine triphosphate (ATP), the molecule that cells use for fuel. In this process, known as aerobic respiration, each glucose molecule yields about 36 molecules of ATP.

S. cerevisiae, however, spurns oxygen. Instead, it converts sugars into ethanol, generating a meagre two molecules of ATP per glucose molecule. Most cells resort to anaerobic respiration only when oxygen is in short supply, but give S. cerevisiae some sugar and it will churn out alcohol even when oxygen is plentiful - sacrificing huge amounts of energy in the process. It is a baffling way to behave, so why does this yeast do it?

By churning out alcohol, yeast sacrifices huge amounts of energy. It's a baffling way to behaveThe story begins back in the Cretaceous period, when tyrannosaurs dominated the land. This was the time when flowering plants began to develop fruits rich in sugars to encourage animals to eat the fruits and disperse their seeds, and among the first to take advantage of this free lunch were the ancestors of S. cerevisiae. These ancient yeasts exploited the fruit sugar in the way you would expect: they used oxygen to break it down into carbon dioxide and water. Some could produce alcohol but they did so only when no oxygen was available. For instance, studies of Candida albicans, which split from the S. cerevisiae lineage well over 100 million years ago, show it has only one "switch" for controlling the genes involved in energy production. This leaves C. albicans with no choice but to respire aerobically if oxygen is available.

Around 80 million years ago, however, something went wrong when one of the ancestors of S. cerevisiae was dividing. One daughter cell got two copies of the genome instead of one. This led to a whole series of genetic changes, including the rewiring of the control circuitry. The yeast that was to become S. cerevisiae became able to turn off the genes for aerobic respiration, giving it the ability to make alcohol even when oxygen is present.

The duplication of the genome also gave the yeast a spare copy of the gene for an enzyme called alcohol dehydrogenase. Before the duplication, the enzyme converted the main breakdown product of sugar, acetaldehyde, into alcohol. We know this thanks to some ingenious work by John Aris of the University of Florida in Gainesville, whose team deduced the most likely DNA sequence of the ancestral enzyme and recreated the protein.

Once S. cerevisiae had two versions of this enzyme, however, they were free to evolve in different directions. One version, ADH1, still performs its original function of converting acetaldehyde into alcohol. The other version, ADH2, does the opposite: it turns alcohol back into acetaldehyde. Unlike ADH1, though, ADH2 is produced only when sugar levels fall.

Put all the pieces together and a clear picture emerges. Ethanol is toxic to most microbes, so acquiring the ability to turn all the glucose available in a fruit into a sea of the stuff gave S. cerevisiae's ancestors a big competitive advantage. "It quickly converts the sugar into something that it can use to defend its territory," says Aris. The yeast itself, of course, has evolved a high tolerance to alcohol.

This strategy would be hugely costly in terms of the energy lost by forgoing aerobic respiration, were it not for ADH2. "Once all the sugar is gone, there's all this ethanol out there," Aris says. The yeast's second trick is to take the ethanol and turn it into acetaldehyde, which it then breaks down using oxygen to reclaim as much energy as possible. "You could say it's delayed gratification," he adds. In short, S. cerevisiae turns sugars into a poison that kills off any rivals, and then feasts on the poison. It's such a successful trick that some other yeasts have evolved a similar strategy, though S. cerevisiae does it best.

The final part of S. cerevisiae's strategy is not so desirable from a drinker's point of view, but our ancestors long ago worked out how to steal the yeast's feast. The simplest way is to drink a fermenting liquid when alcohol levels peak. Better still, the mix can be placed in a sealed container: without oxygen, the yeast cannot feed on the alcohol it has made, and the beverage can last for decades.

The story doesn't end there. Some microbes have evolved to thwart S. cerevisiae's strategy by becoming ethanol-tolerant, and they can ruin a brew by producing unpleasant flavours or turning wine into vinegar. Winemakers add chemicals such as sulphur dioxide to keep these nasties at bay. To reduce the need for such preservatives, some researchers are now working to give yeast extra weapons to do this for themselves. Sakkie Pretorius of the Australian Wine Research Institute in Adelaide, for example, has added genes for microbe-killing proteins taken from the lactic-acid bacteria found in yogurt and from chicken eggs.

There may be many more chapters still to be written in the brewer's tale. But for now let's toast the abilities of Saccharomyces cerevisiae and the pleasure it provides. Cheers everybody!

++++

From issue 2583 of New Scientist magazine, 23 December 2006, page 32-33
It's in our genes
Once yeast had acquired the ability to churn out alcohol, it began to shape the genes of many other creatures, ourselves included.

Primates have long feasted on fruit, and many researchers think that our ancestors evolved to love the scent of alcohol that helped them discover ripe fruit. This could also account for the enjoyment we get from mild inebriation. "The good feeling may have evolved to encourage consumption of ethanol-rich substances," says Robert Dudley at the University of California, Berkeley, who studies the evolution of alcohol consumption.

The big question is how much ethanol our animal relatives consume in the wild. Dudley hopes to find out next year by observing Panamanian spider monkeys eating fruit whose alcohol content he has already measured. Then he has to measure how much ethanol their urine contains. "They're a tricky set of experimental measurements," he says.

While some genes encourage us to seek out alcohol, others deal with the consequences. For instance, like other primates, we have an enzyme called aldehyde dehydrogenase that clears acetaldehyde, a toxic breakdown product of alcohol, from our bodies.

Up to 80 per cent of Han Chinese, Koreans and Japanese, however, have at least one copy of a mutant gene for aldehyde dehydrogenase that makes the enzyme much slower than normal at clearing acetaldehyde from the body. The result is hot flushes and nausea after drinking. This might appear to be a disadvantage, but in fact it is an asset: alcoholism is less common among those with the mutant aldehyde dehydrogenase gene.

This and other mutations that make our bodies less able to deal with alcohol may actually have become more common since we mastered the art of brewing. It seems evolution is calling time on our love affair with booze.

Cheers Ross
 
The big question is how much ethanol our animal relatives consume in the wild. Dudley hopes to find out next year by observing Panamanian spider monkeys eating fruit whose alcohol content he has already measured. Then he has to measure how much ethanol their urine contains. "They're a tricky set of experimental measurements," he says.

This paragraph made me smile :D
 
Can't you just see "Cheif Monkey Piss Collector" on your resume?

Back on topic, the yeast story was a good read.
 
Ross,

I worry about you when you are not crushing grain, you get a bit of spare time and sit down on one of those blue upturned milk crates with a copy 'New Scientist 'and a' pint of Ruination ale' in one hand and and thumb through the pages to read an article about yeast microbes :unsure:

Pumpy ;)
 
Interesting read. Thanks Ross. :super:

I'm not sure about this part though. :angry:

This and other mutations that make our bodies less able to deal with alcohol may actually have become more common since we mastered the art of brewing. It seems evolution is calling time on our love affair with booze.

Not if I can help it. :lol:
 
Up to 80 per cent of Han Chinese, Koreans and Japanese, however, have at least one copy of a mutant gene for aldehyde dehydrogenase that makes the enzyme much slower than normal at clearing acetaldehyde from the body. The result is hot flushes and nausea after drinking. This might appear to be a disadvantage, but in fact it is an asset: alcoholism is less common among those with the mutant aldehyde dehydrogenase gene.

Cheers Ross

One of my Chinese scrap metal customers was over here the other week - He tried my beer & turned bright red, literally. Told me beer always did this to him - reading the above it now make sense - i felt really bad at the time, trouble is he was far too polite to tell me before hand.

Cheers Ross
 
Ross,

I worry about you when you are not crushing grain, you get a bit of spare time and sit down on one of those blue upturned milk crates with a copy 'New Scientist 'and a' pint of Ruination ale' in one hand and and thumb through the pages to read an article about yeast microbes :unsure:

Pumpy ;)

Well, it was that, or sit there lusting after cuckoo clocks :p

Cheers Ross...
 
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