Old yeasts, young beer-The industrial relevance of yeast chronological life span

Abstract

Much like other living organisms, yeast cells have a limited life span, in terms of both the maximal length of time a cell can stay alive (chronological life span) and the maximal number of cell divisions it can undergo (replicative life span). Over the past years, intensive research revealed that the life span of yeast depends on both the genetic background of the cells and environmental factors. Specifically, the presence of stress factors, reactive oxygen species, and the availability of nutrients profoundly impact life span, and signaling cascades involved in the response to these factors, including the target of rapamycin (TOR) and cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathways, play a central role. Interestingly, yeast life span also has direct implications for its use in industrial processes. In beer brewing, for example, the inoculation of finished beer with live yeast cells, a process called "bottle conditioning" helps improve the product's shelf life by clearing undesirable carbonyl compounds such as furfural and 2-methylpropanal that cause staling. However, this effect depends on the reductive metabolism of living cells and is thus inherently limited by the cells' chronological life span. Here, we review the mechanisms underlying chronological life span in yeast. We also discuss how this insight connects to industrial observations and ultimately opens new routes towards superior industrial yeasts that can help improve a product's shelf life and thus contribute to a more sustainable industry.

Keywords: PKA pathway; TORC1/Sch9; bottle conditioning; chronological life span; flavor stability; yeast.

FIGURE 1

The two aging paradigms of Saccharomyces cerevisiae. Chronological aging and the chronological life span (CLS) refer to the time a yeast cell can remain viable in a nondividing state. This G₀‐like state is usually induced by nutrient limitation or external stressors and is characterized by an increased resistance to multiple stressors. Over time, stored carbohydrates become depleted, and the external pH decreases due to the metabolism of ethanol to acetic acid. Combined with cellular damage (e.g., oxidized proteins and mitochondrial damage) that inevitably arises upon extended survival, these environmental factors ultimately lead to cell lysis. Replicative aging and replicative life span (RLS) refer to how many doublings a mother cell can undergo before senescence. This number is limited due to extrachromosomal ribosomal DNA circles, oxidized proteins, and damaged mitochondria that accumulate over time. Upon division, the damage is asymmetrically inherited by the mother cell, which allows the daughter cells to reset their replicative capacity, irrespective of the RLS of the mother cell

FIGURE 2

Major pathways driving chronological life span. Both the TORC1/Sch9 and PKA pathways are responsive to the availability of nutrients in the environment. Upon nutrient restriction, they are downregulated and allow the central protein kinase Rim15 to activate the stress responsive transcription factors Gis1 and Msn2/4. Together, these pathways orchestrate the cellular stress responses through increased transcription of, among others, heat shock proteins, trehalose synthase, autophagy‐related genes, and detoxifying enzymes such as Sod2 and Ctt1. During growth, reduced TORC1/Sch9 signaling also upregulates mitochondrial respiration and consequently increases the formation of ROS. This stimulates an adaptive response that decreases ROS production during chronological aging. Together, these cellular changes result in an increased chronological life span

FIGURE 3

Overview of the mechanisms through which Saccharomyces cerevisiae can slow down beer aging. Left: Sulfite is formed as an intermediate during cysteine and methionine synthesis. Next to its role as an antioxidant, sulfite can form adducts with staling aldehydes, thus preventing them from staling the beer. Top: Coenzyme regeneration allows aldoketoreductase enzymes to convert flavor‐negative aldehydes to their corresponding, less flavor‐active alcohols. Right: By scavenging residual oxygen, S. cerevisiae can prevent oxidative reactions from both degrading beneficial aroma compounds and formation of undesired carbonyl compounds. An example of the ROS‐mediated oxidation of ethanol (quantitatively the most important alcohol) to acetaldehyde is also shown