Adaptive Response and Tolerance to Acetic Acid in Saccharomyces cerevisiae and Zygosaccharomyces bailii: A Physiological Genomics Perspective

Abstract

Acetic acid is an important microbial growth inhibitor in the food industry; it is used as a preservative in foods and beverages and is produced during normal yeast metabolism in biotechnological processes. Acetic acid is also a major inhibitory compound present in lignocellulosic hydrolysates affecting the use of this promising carbon source for sustainable bioprocesses. Although the molecular mechanisms underlying Saccharomyces cerevisiae response and adaptation to acetic acid have been studied for years, only recently they have been examined in more detail in Zygosaccharomyces bailii. However, due to its remarkable tolerance to acetic acid and other weak acids this yeast species is a major threat in the spoilage of acidic foods and beverages and considered as an interesting alternative cell factory in Biotechnology. This review paper emphasizes genome-wide strategies that are providing global insights into the molecular targets, signaling pathways and mechanisms behind S. cerevisiae and Z. bailii tolerance to acetic acid, and extends this information to other weak acids whenever relevant. Such comprehensive perspective and the knowledge gathered in these two yeast species allowed the identification of candidate molecular targets, either for the design of effective strategies to overcome yeast spoilage in acidic foods and beverages, or for the rational genome engineering to construct more robust industrial strains. Examples of successful applications are provided.

Physiological responses of Saccharomyces cerevisiae to industrially relevant conditions: Slow growth, low pH, and high CO2 levels

“…The complexity of the observed physiological and transcriptional responses indicates that improving robustness under industrial conditions is unlikely to be achieved by individual genetic modifications. Instead, exploration of yeast biodiversity (Palma, Guerreiro, & Sá-Correia, 2018), evolutionary engineering (Mans, Daran, & Pronk, 2018) and/or genome-shuffling approaches (Magocha et al, 2018;Steensels, Gorkovskiy, & Verstrepen, 2018) may offer interesting possibilities.…”

Production of mannosylerythritol lipids from lignocellulose hydrolysates: tolerance thresholds of Moesziomyces antarcticus to inhibitors

“…[18][19][20][21][22] In their undissociated form, these organic small acids are able to passively diffuse across the cell membrane of S. cerevisiae. 19,23,24 However, the pH of the fermentation broth used in the current work was 6, well above the pKa of acetic (4.75) and formic acid (3.75), and thus in the culture, these acids were mainly in their dissociated form, acetate (>94.6%) and formate (>99.4%). It was observed for S. cerevisiae that acetate can be transported into the cell through an acetate carrier (Ady2) where it will accumulate, causing turgor pressure and oxidative stress.…”

“…It was observed for S. cerevisiae that acetate can be transported into the cell through an acetate carrier (Ady2) where it will accumulate, causing turgor pressure and oxidative stress. 23 However, for M. antarcticus, and some oleaginous yeasts, [19][20][21] for culture pH above pKa, a tolerance to acetate has been observed. A previous study, using 13 C labelled acetate, report that 36% of the synthesized lipids by the oleaginous yeast Mortierella isabelline were derived from acetate added to culture at 2.0 g L −1 .…”

Improved bioconversion of lignocellulosic biomass by Saccharomyces cerevisiae engineered for tolerance to acetic acid

“…Notably, using an evolutionary engineering approach, we successfully obtained an evolved yeast strain, XUSAE57, tolerant to acetic acid by enhancing bioconversion of lignocellulosic biomass into bioethanol with significantly improved bioconversion rates and the highest yield ever reported. Sedlak and Ho (2004) Based on the prior knowledge, the stressed cells employ an energy-intensive mechanism to maintain the intracellular pH homeostasis by pumping out the excess protons through membrane H + -ATPases at the expense of ATP, which ultimately compromises cell growth (Palma, Guerreiro, & Sa-Correia, 2018;Pampulha & Loureiro-Dias, 2000;Ullah, Chandrasekaran, Brul, & Smits, 2013). However, the RNAsequencing results did not support the previously hypothesized molecular mechanisms of acetic acid detoxification in the acetic acid-stressed and evolved S. cerevisiae cells.…”

“…Based on the prior knowledge, the stressed cells employ an energy‐intensive mechanism to maintain the intracellular pH homeostasis by pumping out the excess protons through membrane H + ‐ATPases at the expense of ATP, which ultimately compromises cell growth (Palma, Guerreiro, & Sa‐Correia, ; Pampulha & Loureiro‐Dias, ; Ullah, Chandrasekaran, Brul, & Smits, ). However, the RNA‐sequencing results did not support the previously hypothesized molecular mechanisms of acetic acid detoxification in the acetic acid‐stressed and evolved S. cerevisiae cells.…”