The yeast is yet to come

18 March 2018
​Although it may seem like just another mundane fungus, yeast plays a leading part in many VIB studies. Some scientists use it as a model for tumor cells, while others aim at uncovering the genes of specific yeast strains to find out where flavors come from. Whatever the research goal, yeast often comes in handy.

Last fall the Johan Thevelein group from the VIB-KU Leuven Center for Microbiology relied on yeast cells
to suggest a possible relationship between sugar and cancer, and during the same period, they also identified the yeast genes behind rose and honey flavors in beer and wine.

The Warburg effect
After nine years of joint effort alongside Wim Versées and Peter Tompa from the VIB-VUB Center for Structural Biology and Veerle Janssens (KU Leuven), Johan and his team were able to provide evidence for
the positive correlation between sugar and cancer. They discovered that a major intermediate of sugar breakdown, fructose-1,6-bisphosphate, is a potent stimulator of the Ras proteins, which in overactive
form are well-known activators of cancer. Their study is published in Nature Communications.

Frederik Van Leemputte (PhD student and cofirst author of this publication): “Our research mainly focused on how the Warburg effect, the phenomenon in which cancer cells rapidly break down sugar, stimulates tumor growth. It was already well known that the stronger the Warburg effect, the more aggressive the tumor becomes. For the first time we have now identified a logical molecular explanation for this correlation.”

As you might have guessed, yeast cells proved to be the key to these results. Yeast contains the same Ras
proteins that are commonly found in mammalian cells, which can cause cancer in their mutated form. Moreover, just like cancer cells, yeast has a preference for breakdown of sugar by fermentation rather than respiration. The fungus is therefore an attractive model organism for cancer research. “We observed that sugar degradation is linked to the activation of Ras proteins, stimulating the multiplication of both yeast and cancer cells,”

Johan explains. “Although it’s still too early to make statements about the possible consequences for cancer treatments and adjusted diets, our discovery delivers very valuable novel insights.”

A molecular whiff
In the very same lab, postdoctoral fellow Maria Remedios Foulquié-Moreno investigates how specific yeast strains shape the flavors in beer and wine. Maria: “Although most aromas in wines come from the grapes, the metabolism of yeast can alter those, adding secondary flavors. And the yeast itself also contributes its own flavors. In beer, yeast is the main source of the aroma produced during fermentation.”

Using their polygenic analysis platform and the CRISPR/Cas9 technology, Maria and her colleagues have now identified the specific yeast genes that produce high levels of phenylethyl acetate (2-PEAc). The name of this compound may not ring a bell, but the aroma probably does. Maria: “When a wine smells of roses or honey, this is mainly caused by 2-PEAc.”

However, why some yeasts produce more of this compound than others remained unknown – until now. Maria: “We found that two genes – TOR1 and FAS2 – were directly related to the high production of 2-PEAc. This was quite unexpected, as neither of them had been associated with this rose-like aroma before.”

These findings may be used to grow yeasts that produce new flavors. Maria: “In the past, enhancing industrial strains for desirable aromas has been a real challenge. Scientists usually rely on cross-breeding to select specific genes, but this is time-consuming, expensive, and may cause other unwanted changes in the yeast. By using the CRISPR/Cas9 technology, we can now engineer production of desirable aromas without affecting
other traits.”

Peeters, Van Leemputte, Fischer et al. Nature Communications, 2017
Trindade de Carvalho et al. mBio 2017

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Frederik Van Leemputte, Johan Thevelein and Maria Remedios Foulquié Moreno