AUTHOR=Shin Minhye , Park Heeyoung , Kim Sooah , Oh Eun Joong , Jeong Deokyeol , Florencia Clarissa , Kim Kyoung Heon , Jin Yong-Su , Kim Soo Rin 

TITLE=Transcriptomic Changes Induced by Deletion of Transcriptional Regulator GCR2 on Pentose Sugar Metabolism in Saccharomyces cerevisiae

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2021.654177

DOI=10.3389/fbioe.2021.654177

ISSN=2296-4185

ABSTRACT=<p>Being a microbial host for lignocellulosic biofuel production, <italic>Saccharomyces cerevisiae</italic> needs to be engineered to express a heterologous xylose pathway; however, it has been challenging to optimize the engineered strain for efficient and rapid fermentation of xylose. Deletion of <italic>PHO13</italic> (Δ<italic>pho13</italic>) has been reported to be a crucial genetic perturbation in improving xylose fermentation. A confirmed mechanism of the Δ<italic>pho13</italic> effect on xylose fermentation is that the Δ<italic>pho13</italic> transcriptionally activates the genes in the non-oxidative pentose phosphate pathway (PPP). In the current study, we found a couple of engineered strains, of which phenotypes were not affected by Δ<italic>pho13</italic> (Δ<italic>pho13</italic>-negative), among many others we examined. Genome resequencing of the Δ<italic>pho13</italic>-negative strains revealed that a loss-of-function mutation in <italic>GCR2</italic> was responsible for the phenotype. Gcr2 is a global transcriptional factor involved in glucose metabolism. The results of RNA-seq confirmed that the deletion of <italic>GCR2</italic> (Δ<italic>gcr2</italic>) led to the upregulation of PPP genes as well as downregulation of glycolytic genes, and changes were more significant under xylose conditions than those under glucose conditions. Although there was no synergistic effect between Δ<italic>pho13</italic> and Δ<italic>gcr2</italic> in improving xylose fermentation, these results suggested that <italic>GCR2</italic> is a novel knockout target in improving lignocellulosic ethanol production.</p>