Multi-Faceted Systems Biology Approaches Present a Cellular Landscape of Phenolic Compound Inhibition in Saccharomyces cerevisiae

Abstract

Synthetic biology has played a major role in engineering microbial cell factories to convert plant biomass (lignocellulose) to fuels and bioproducts by fermentation. However, the final product yield is limited by inhibition of microbial growth and fermentation by toxic phenolic compounds generated during lignocellulosic pre-treatment and hydrolysis. Advances in the development of systems biology technologies (genomics, transcriptomics, proteomics, metabolomics) have rapidly resulted in large datasets which are necessary to obtain a holistic understanding of complex biological processes underlying phenolic compound toxicity. Here, we review and compare different systems biology tools that have been utilized to identify molecular mechanisms that modulate phenolic compound toxicity in Saccharomyces cerevisiae. By focusing on and comparing functional genomics and transcriptomics approaches we identify common mechanisms potentially underlying phenolic toxicity. Additionally, we discuss possible ways by which integration of data obtained across multiple unbiased approaches can result in new avenues to develop yeast strains with a significant improvement in tolerance to phenolic fermentation inhibitors.

Comparative chemical genomic profiling across plant-based hydrolysate toxins reveals widespread antagonism in fitness contributions

“…First, Saccharomyces cerevisiae cannot natively ferment pentoses and oligosaccharides released from deconstructed plant biomass, thereby underutilizing a significant carbon fraction (Kricka et al 2015 , Zhao et al 2020 ). Second, toxins found in processed plant biomass are stressful to biofuel microbes, and stress responses mounted by cells redirect resources away from bioproduct formation (Palmqvist and Hahn-Hägerdal 2000 , Almeida et al 2007 , Liu 2011 , Piotrowski et al 2014 , Cunha et al 2019 , Fletcher and Baetz 2020 ). Thus, a major goal in sustainable biofuel research is to engineer pentose-consuming microbes that are resilient to toxins derived from lignocellulose and pretreatment processes.…”

“…Several studies have investigated the response to particular hydrolysate toxins, including phenolic compounds (Fletcher and Baetz 2020 ), ionic liquids (Kumari et al 2020 ), or various other classes of compounds (Jönsson and Martín 2016 , Kim 2018 , Li et al 2022 ). Yet much remains unknown about mechanisms of toxicity and how to overcome them, especially for sets of toxins variably found together and under anaerobic conditions, which is preferred for the industrial production of fermentative biofuels.…”

Investigating the Efficiency of Hydroxycinnamic Acids to Inhibit the Production of Enniatins by Fusarium avenaceum and Modulate the Expression of Enniatins Biosynthetic Genes

“…According to Kulik et al [19], some phenolic acids could trigger a stimulation of the biosynthesis of ergosterol in F. graminearum and F. culmorum. An upregulation of ergosterol biosynthetic genes upon phenolic exposure has also been reported to explain the tolerance of Saccharomyces cerevisiae [32]. To try deciphering the origin of the growth increasing effects that we have observed in the present study, it would be worth investigating the impact of FER, CAF, and COUM exposure on the biosynthesis of ergosterol in F. avenaceum.…”

In Vitro Activity of Selected Phenolic Compounds against Planktonic and Biofilm Cells of Food-Contaminating Yeasts

“…Investigation of phenolic tolerance mechanisms in yeasts is a growing research area nowadays. In such studies, the use of functional genomics tools, such as chemogenomic screens will help researchers to better understand the key factors associated with the phenolics tolerance in food spoilage yeasts [ 47 ].…”