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How Ancient Sake Brewers Tamed a Fungus

Jesse Jenkins

A new comparative genetic study suggests that ancient sake brewers evolved a toxin-producing wild fungus into an alcohol producing by selecting desired genetic variants.

We’ve done it with plants and animals. Most of the time, it’s involved some aspect of their morphology, such as the introduction or exaggeration of some physical trait for our benefit through artificial selection. But with fungi, domestication is different.

Aspergillus oryzae, on the left, has been genetically optimized to convert rice starch into sugars. By contrast its wild cousin, Aspergillus flavus, is a major agricultural pest and produces aflatoxin, a potent natural carcinogen. Source: John Gibbons / Vanderbilt

In a paper published in the journal Current Biology on July 12, Vanderbilt researchers conducted a comparative genomic study of two closely related but very differently functioning fungi—the domesticated Aspergillus oryzae, which is used in sake production, and its wild and harmful relative Aspergillus flavus, which produces a powerful natural carcinogen called aflatoxin. In the end, the study highlights a major difference between the domestication of microbes and that of plants and animals.

“If you think of the classic case of domestication in plants and animals, they involved a lot of changes in morphology,” said Antonis Rokas, assistant professor of biological sciences at Vanderbilt University. “But, in fungi, what we’re seeing for the first time, is that almost entirely all the changes are changes in metabolism. So, there’s change in the physiology much more in microbes than in development.”

In the paper, Rokas and his team propose that a thousand years ago, A. oryzae was once a toxigenic microbe that more closely resembled A. flavus than today’s strains do. But that was before sake brewers began working with the fungus, turning A. oryzae into a cell factory to produce the enzymes and metabolites that are necessary to breakdown rice starch into sugar, which is then converted into alcohol by yeast. Through this artificial selection process, the genes involved in sugar production were upregulated, while the genes involved in the production of toxins were down-regulated.

“We think that part of the reason is that when you make sake, you actually have together both A. oryzae and Saccharomyces cerevisiae, the yeast that makes the alcohol. So, this coexistence has selected for A. oryzae to act friendly to the yeast,” said Rokas.

To perform the comparative genetic analysis, Rokas and his team collected genomic data that described the variation between both A. oryzae as well as its wild relative. They then collected gene expression data for some strains of both species when grown on rice. Finally, as part of their three-layer analysis, the lab collected proteomic data that showed the abundance of particular proteins during growth on rice again from each of the fungi.

“The main challenge was distilling down and trying to find the biology amidst these really huge data sets. We were dealing with gigabytes of data, but we’re lucky enough to have a super computer so the majority of the analysis was done there,” said Rokas.

To gain a better understanding about the process of microbial domestication, Rokas plans to study several other domesticated microbes. “In the way that we have a sort of consensus on the process of domestication of several different plants and animals, it would be nice to get the same kind of consensus or picture of how the domestication process works in microbes,” said Rokas.

Keywords:  sake microbiology microbes