SUMO expression shortens the lag phase of Saccharomyces cerevisiae yeast growth caused by complex interactive effects of major mixed fermentation inhibitors found in hot-compressed water-treated lignocellulosic hydrolysate

Significance statement

Degradation of lignocellulosic material generates complex inhibitors, which is a technical barrier for production of useful materials using fermentation microbes. We have found that glycolaldehyde is a potent fermentation inhibitor. In this invention, we discovered that SUMOylation occurred in the presence of fermentation inhibitors and was a key factor conferring tolerance to complex effect of fermentation inhibitors. The lag phase of growth could be shortened by introducing the SUMOylation pathway into yeast strains. These findings provide a novel platform for engineering yeast strains to overcome one of the key barriers for utilization of lignocellulosic material.


SUMO expression shortens the lag phase of Saccharomyces cerevisiae yeast growth caused by complex interactive effects of major mixed fermentation inhibitors found ..

Journal Reference

Applied Microbiology and Biotechnology, January 2015, Volume 99, Issue 1, pp 501-515.

Lahiru N. Jayakody, Masafumi Kadowaki, Keisuke Tsuge, Kenta Horie, Akihiro Suzuki, Nobuyuki Hayashi, Hiroshi Kitagaki.

  1. Department of Biochemistry and Applied Biosciences, United Graduate School of Agricultural Sciences, Kagoshima University, 1-21-24, Korimoto, Kagoshima City, Kagoshima, 890-8580, Japan and
  2. Department of Environmental Sciences, Faculty of Agriculture, Saga University, Saga, 840-8502, Japan and
  3. Industrial Technology Center of Saga, 114 Yaemizo, Saga, 849-0932, Japan and
  4. Department of Applied Biochemistry and Food Science, Faculty of Agriculture, Saga University, Saga, 840-8502, Japan.



The complex inhibitory effects of inhibitors present in lignocellulose hydrolysate suppress the ethanol fermentation of Saccharomyces cerevisiae. Although the interactive inhibitory effects play important roles in the actual hydrolysate, few studies have investigated glycolaldehyde, the key inhibitor of hot-compressed water-treated lignocellulose hydrolysate. Given this challenge, we investigated the interactive effects of mixed fermentation inhibitors, including glycolaldehyde. First, we confirmed that glycolaldehyde was the most potent inhibitor in the hydrolysate and exerted interactive inhibitory effects in combination with major inhibitors. Next, through genome-wide analysis and megavariate data modeling, we identified SUMOylation as a novel potential mechanism to overcome the combinational inhibitory effects of fermentation inhibitors. Indeed, overall SUMOylation was increased and Pgk1, which produces an ATP molecule in glycolysis by substrate-level phosphorylation, was SUMOylated and degraded in response to glycolaldehyde. Augmenting the SUMO-dependent ubiquitin system in the ADH1-expressing strain significantly shortened the lag phase of growth, released cells from G2/M arrest, and improved energy status and glucose uptake in the inhibitor-containing medium. In summary, our study was the first to establish  SUMOylation as a novel platform for regulating the lag phase caused by complex fermentation inhibitors.

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