Distinguishing genuine resistance from innate stress response to furfural and HMF stress using molecular phenotypes for the industrial yeast Saccharomyces cerevisiae

Authors: Liu, Zonglin

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 3/18/2019
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Industrial yeast Saccharomyces cerevisiae is a workhorse widely applied in fermentation-based industrial applications. Type strain NRRL Y-12632 is more resistance to varied environmental conditions in general than most other strains. However, it cannot survive challenge of synergistic toxicity of 2-furaldehyde (furfural) and 5-hydroxymethyl-2-furaldehdye (HMF). Using Y-12632 as a progenitor, a more tolerant strain of NRRL Y-50049 was obtained, which is resistant to numerous toxic chemicals and able to detoxify furfural and HMF in situ while producing ethanol. The tolerant characteristics of Y-50049 is inheritable and stable over a decade. Transient induced gene expression in response to toxic chemicals, often represents an innate stress response with limited tolerance. However, it is commonly used to identify tolerant genes and often fails subsequent genetic engineering efforts for resistant strain development. This study investigates molecular phenotypes in response to furfural-HMF challenge for Y-50049 and its progenitor Y-12632 by comparative transcriptomic and proteomic analyses using a time course study. Both strains showed the same growth curve and essentially the same protein expression profiles in the absence of furfural-HMF. However, Y-50049 displayed more than 200 genes showing higher levels of transcription abundance without furfural-HMF treatment, namely enhance transcription background (ETB). Many genes with ETB showed continued increased expressions over time in response to furfural-HMF challenge. The number of genes showing higher levels of transcription fluctuated during the dynamic transcription process in lag phase. Yet the high levels of transcription abundance were consistent. While both strains share some increased expressions involving critical functions, the increased transcription levels in Y-50049 were always higher than those in its progenitor Y-12632. Several pathway-based transcription profiles, such as reprogrammed detoxification pathway, enhanced enzymatic and nonenzymatic defense systems, and sulfur amino acid biosynthesis superpathway, were identified supported by both gene expression and protein expression evidence. These findings clearly distinguished the adapted resistance in Y-50049 from the innate stress response of Y-12632. Outcomes of this study deepen understanding of mechanisms of adapted resistance and provide a trustworthy reference of dependable candidate genes for new strain development.