AUTHOR=Liu Chen-Guang , Li Kai , Li Ke-Yi , Sakdaronnarong Chularat , Mehmood Muhammad Aamer , Zhao Xin-Qing , Bai Feng-Wu 

TITLE=Intracellular Redox Perturbation in Saccharomyces cerevisiae Improved Furfural Tolerance and Enhanced Cellulosic Bioethanol Production

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=8

YEAR=2020

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2020.00615

DOI=10.3389/fbioe.2020.00615

ISSN=2296-4185

ABSTRACT=<p>Furfural is a major toxic byproduct found in the hydrolysate of lignocellulosic biomass, which adversely interferes with the growth and ethanol fermentation of <italic>Saccharomyces cerevisiae</italic>. The current study was focused on the impact of cofactor availability derived intracellular redox perturbation on furfural tolerance. Here, three strategies were employed in cofactor conversion in <italic>S. cerevisiae</italic>: (1) heterologous expression of NADH dehydrogenase (<italic>NDH</italic>) from <italic>E. coli</italic> which catalyzed the NADH to NAD<sup>+</sup> and increased the cellular sensitivity to furfural, (2) overexpression of <italic>GLR1, OYE2, ZWF1</italic>, and <italic>IDP1</italic> genes responsible for the interconversion of NADPH and NADP<sup>+</sup>, which enhanced the furfural tolerance, (3) expression of NAD(P)<sup>+</sup> transhydrogenase (<italic>PNTB</italic>) and NAD<sup>+</sup> kinase (<italic>POS5</italic>) which showed a little impact on furfural tolerance. Besides, a substantial redistribution of metabolic fluxes was also observed with the expression of cofactor-related genes. These results indicated that NADPH-based intracellular redox perturbation plays a key role in furfural tolerance, which suggested single-gene manipulation as an effective strategy for enhancing tolerance and subsequently achieving higher ethanol titer using lignocellulosic hydrolysate.</p>