APPLICATIONS OF TECHNOLOGY:
- Biological production of higher alcohols
- Increased isopentenol yields in aerobic and anaerobic conditions
- Higher efficiency and lower costs
- Optimized for oxygen-limited conditions
- Enables production at fermentor scale
- Better host cell growth
Researchers at the Joint BioEnergy Institute (JBEI) have developed two novel biosynthesis pathways for five-carbon alcohol (isopentenol or 3-methyl-3-buten-1-ol) from mevalonate that reduce the energy demand and cost of earlier applications of the mevalonate pathway by using genetically engineered host cells, whose culturing stage can happen both in anaerobic or aerobic conditions. This invention can be used in an industrial scale, even under oxygen-limited conditions.
The first pathway produces isopentenol directly from mevalonate. The second pathway introduces a novel phosphatase to produce isopentenol. Through the implementation of the engineered host cells, the novel pathways bypass the phosphorylation reactions by mevalonate kinase (MK) and/or phosphomevalonate kinase (PMK). This increases the energy efficiency by diminishing the ATP demand by one to two ATP, decreases the cost of protein synthesis by diminishing the number of enzymes by two to three and relieves the process from isopentenyl diphosphate (IPP) toxicity by avoiding IPP biosynthesis. The developed pathways can be further enhanced for oxygen-limited conditions by optimizing cofactors for redox balance of top portion enzymes. This relieves the need of aeration during fermentation and lowers the operation cost in industrial scale production.
DEVELOPMENT STAGE: Proven principle. For a table indicating isopentenol production per OD of the original pathway and the new pathway, go here.
STATUS: Patent issued: U.S. patent no. 10814724. Available for licensing or collaborative research.
FOR MORE INFORMATION:
Kang, A., George, K. W., Wang, G., Baidoo, E., Keasling, J. D., Lee, T. S. “Isopentenyl diphosphate (IPP)-bypass mevalonate pathways for isopentenol production,” Metabolic Engineering, 34 (2016), 25-35..
REFERENCE NUMBER: 2014-135