Systems Biology Analysis of Zymomonas mobilis ZM4 Ethanol Stress Responses

Abstract

Background Zymomonas mobilis ZM4 is a capable ethanologenic bacterium with high ethanol productivity and ethanol tolerance. Previous studies indicated that several stress-related proteins and changes in the ZM4 membrane lipid composition may contribute to ethanol tolerance. However, the molecular mechanisms of its ethanol stress response have not been elucidated fully.Methodology/Principal FindingsIn this study, ethanol stress responses were investigated using systems biology approaches. Medium supplementation with an initial 47 g/L (6% v/v) ethanol reduced Z. mobilis ZM4 glucose consumption, growth rate and ethanol productivity compared to that of untreated controls. A proteomic analysis of early exponential growth identified about one thousand proteins, or approximately 55% of the predicted ZM4 proteome. Proteins related to metabolism and stress response such as chaperones and key regulators were more abundant in the early ethanol stress condition. Transcriptomic studies indicated that the response of ZM4 to ethanol is dynamic, complex and involves many genes from all the different functional categories. Most down-regulated genes were related to translation and ribosome biogenesis, while the ethanol-upregulated genes were mostly related to cellular processes and metabolism. Transcriptomic data were used to update Z. mobilis ZM4 operon models. Furthermore, correlations among the transcriptomic, proteomic and metabolic data were examined. Among significantly expressed genes or proteins, we observe higher correlation coefficients when fold-change values are higher.ConclusionsOur study has provided insights into the responses of Z. mobilis to ethanol stress through an integrated “omics” approach for the first time. This systems biology study elucidated key Z. mobilis ZM4 metabolites, genes and proteins that form the foundation of its distinctive physiology and its multifaceted response to ethanol stress.

Discovery of Ethanol-Responsive Small RNAs in Zymomonas mobilis

“…Therefore, we systematically tested expression levels of all identified sRNA candidates under the ethanol stress conditions. We chose a 5% (vol/vol) ethanol supplement to the medium as the ethanol stress conditions given that 6% (vol/vol) ethanol was previously shown to affect cell viability dramatically (44). We confirmed that Zms2, Zms6, and Zms18 showed differential expression under ethanol stress conditions (Fig.…”

“…Most of the newly found genes in our study are related to metabolism and cellular processes. Our analysis showed that alcohol dehydrogenase, which was downregulate under ethanol treatment conditions (44), was less abundant in late exponential phase under aerobic conditions (see Table S5). We also confirmed that the Hfq gene (ZMO0347) was more abundant under anaerobic conditions.…”

High tolerance and physiological mechanism of Zymomonas mobilis to phenolic inhibitors in ethanol fermentation of corncob residue

“…It demonstrated the high ethanol fermentability (ethanol yield above 75% and productivity above 1.1 g/L/h) and strong tolerance to high temperature (42°C), high lignocellulosic solids loading (35%), and inhibitors (acetic acid, furfural, and HMF) during the simultaneous saccharification and fermentation of the pretreated corn stover, wheat straw, rice straw and other agricultural biomass (Chu et al, ; Zhang et al, , ). Although Z. mobilis demonstrates advantages in ethanol fermentation (Yang et al, ), the low tolerance to inhibitory compounds makes it is less frequently used when the inhibitor is at a high level (Su et al, ; Zhang and Lynd, ). The tolerance of Z. mobilis to furans and weak acids had been investigated extensively (Dong et al, ; Skerker et al, ; Yang et al, , ), but few studies focus on the toxic effect of phenolic inhibitors on Z. mobilis .…”

Identification and characterization of ethanol‐inducible promoters of Zymomonas mobilis based on omics data and dual reporter–gene system

“…Systems biology datasets published for Z. mobilis were collected and analyzed to identify the potential ethanol‐inducible promoters. Since Z. mobilis produces ethanol gradually, which usually reaches the peak when entering the stationary phase with the consumption up of carbon sources such as glucose, native ethanol‐inducible promoters probably can be identified by selecting differentially expressed genes at the late stationary growth stage or under ethanol stress conditions . Genes with at least twofold changes in these conditions were selected for Veen analysis to identify common genes, and promoters of these genes were considered as candidate‐inducible promoters (Fig.…”

“…Control1, p1ZMRG, and p2ZMRG represent the control which cultured in normal condition. Log represents exponential phase, Sta represents stationary phase, EtOH means ethanol‐induced conditions .…”