1. Regulatory Mechanism of Alcoholic Fermentation

Yeast’s alcoholic fermentation is one of the most familiar microbial metabolic functions to mankind, having been used since prehistoric times to produce alcoholic beverages, fermented foods, bioethanol, and other products. Through years of accumulated research, the enzymes that catalyze each metabolic reaction and the genes that encode them have all been elucidated. In today’s age of synthetic biology, biomanufacturing technology that improves the production capacity of useful substances is becoming a universal methodology. Therefore, people tend to think that it is possible to freely modify the alcoholic fermentation of yeast, but in reality, it is surprisingly difficult and there is currently no way to achieve this goal. The fermentation and brewing industries still use traditional techniques that only control the life and death of yeast by controlling temperature and nutrient sources. The question is how to modify the alcohol fermentation capacity per cell.

We have focused on the high alcohol fermentation ability of sake yeast, an endemic industrial microorganism in Japan. Omics analysis of sake yeast revealed a mutation that is unique to sake yeast among various yeasts in the world. When this mutation is introduced into a laboratory yeast with low alcohol fermentation capacity, it is possible to obtain a high alcohol fermentation capacity comparable to that of sake yeast (Fig. 1). By applying this technology, it is possible to modify the alcohol fermentation ability of various yeasts used in the fermentation and brewing industries as desired. In fact, we have succeeded in improving the alcoholic fermentation ability of bioethanol yeast and beer yeast (Fig. 2), and conversely, by suppressing the alcoholic fermentation of sake yeast, it has become possible to create a yeast suitable for low-alcohol sake production. We will continue to clarify the genes that play a key role in the regulatory mechanism of alcohol fermentation and establish our own “alcohol fermentation design technology” by modifying these genes.

【Related Papers】

  1. D. Watanabe*, M. Kawashima, N. Yoshioka, Y. Sugimoto, H. Takagi; Rational design of alcoholic fermentation targeting extracellular carbon. NPJ Sci. Food 7(1): 37 (2023)
  2. D. Watanabe*, T. Kajihara, Y. Sugimoto, K. Takagi, M. Mizuno, Y. Zhou, J. Chen, K. Takeda, H. Tatebe, K. Shiozaki, N. Nakazawa, S. Izawa, T. Akao, H. Shimoi, T. Maeda, H. Takagi; Nutrient Signaling via the TORC1-Greatwall-PP2AB55δ pathway is responsible for the high initial rates of alcoholic fermentation in sake yeast strains of Saccharomyces cerevisiae. Appl. Environ. Microbiol. 85: e02083-18 (2019)
  3. D. Watanabe, Y. Zhou, A. Hirata, Y. Sugimoto, K. Takagi, T. Akao, Y. Ohya, H. Takagi, H. Shimoi*; Inhibitory role of Greatwall-like protein kinase Rim15p in alcoholic fermentation via upregulating the UDP-glucose synthesis pathway in Saccharomyces cerevisiae. Appl. Environ. Microbiol. 82: 340-351 (2016)
  4. D. Watanabe, Y. Araki, Y. Zhou, N. Maeya, T. Akao, H. Shimoi*; A loss-of-function mutation in the PAS kinase Rim15p is related to defective quiescence entry and high fermentation rates of Saccharomyces cerevisiae sake yeast strains. Appl. Environ. Microbiol. 78: 4008-4016 (2013)
  5. D. Watanabe, H. Wu, C. Noguchi, Y. Zhou, T. Akao, H. Shimoi*; Enhancement of the initial rate of ethanol fermentation due to dysfunction of yeast stress response components Msn2p and/or Msn4p. Appl. Environ. Microbiol. 77: 934-941 (2011)