Advantages
- Increased Productivity: ATP regeneration using light energy compensates for intracellular energy shortages—a rate-limiting factor in bioprocesses—without disrupting the natural metabolism of microorganisms.
- Versatile Target Systems and Hosts: A mutant rhodopsin library is currently under construction to cater to various production systems and host organisms.
Technology Overview & Background
Bioprocesses, which utilize biological reactions for substance production, are anticipated to significantly reduce CO₂ emissions compared to conventional chemical processes. This is because bioprocesses can operate at room temperature and normal pressure, unlike chemical processes that typically require high temperatures and pressures. Furthermore, while chemical processes often involve multiple complex reaction stages, bioprocesses leverage efficient intracellular metabolic pathways, making them particularly advantageous in the production of complex compounds with high carbon content. As a result, the bioprocess market is expected to expand, attracting large-scale investments and active research and development aimed at practical applications. However, increasing the productivity of bioprocesses accelerates the consumption of ATP, an essential energy source for metabolic reactions and substance synthesis. This often leads to productivity limitations due to ATP depletion. In addition, ATP deficiency negatively impacts cell growth and stress tolerance, ultimately reducing overall process efficiency.
To address these challenges, the inventors have focused on bacterial rhodopsins. Rhodopsin functions as an ion channel in the cell membrane, utilizing light energy to expel protons from the cell. For ATP synthesis, cells require protons from the extracellular environment. By introducing rhodopsin into the host, protons are actively expelled from the cell, enabling ATP synthase to efficiently recapture protons and regenerate ATP (refer to the figure below). This mechanism compensates for ATP deficiencies and significantly boosts the productivity of target substances. Additionally, through genetic modifications to improve rhodopsin’s functionality, ongoing development efforts aim to further enhance productivity and cell growth.
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Fig. Light-driven ATP regenerating system
Data
The introduction of rhodopsin R17 and its mutants (R17-N1, R17-N2, R17-N11) into E. coli for glutathione (GSH) production resulted in the R17-N1 mutant significantly enhancing both GSH concentration and intracellular content. (see figure)
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Publications
- Toya, Y., Hara, K. Y., et al. Metabolic Engineering, Volume 72, July 2022, Pages 227-236.
[DOI]: https://doi.org/10.1016/j.ymben.2022.03.012
Patents
JP2022-162218, US18/045012, EP.22200274.A
Principal Investigator & Academic Institution
Associate Prof. Kiyotaka Y. Hara (Department of Environmental and Life Sciences, School of Food and Nutritional Sciences, University of Shizuoka)
Expectations
TECH MANAGE are seeking companies interested in this research project. To promote the societal implementation of this technology, the inventors have established 396bio (396bio Co., Ltd.). We aim to accelerate research and development in collaboration with companies interested in this innovative solution.
Please feel free to contact us for possibility to schedule a direct meeting with our researchers or to discuss the disclosure of unpublished data under a nondisclosure agreement with the University of Shizuoka.
Project No.TT-05167