Kobe University Engineers Yeast for Herbal Medicine Production

A Kobe University research team has modified yeast cells to produce high concentrations of a valuable medicinal compound, paving the way for more accessible, scalable production of plant-derived substances.

Overcoming challenges in mass-producing herbal compounds

Many herbal compounds with medicinal properties are not feasible for large-scale production. One such compound, artepillin C, is known for its antimicrobial, anti-inflammatory, antioxidant and anticancer effects but is typically obtained in small quantities as a bee byproduct. Kobe University bioengineers aimed to address these limitations by using microbial production methods, which could increase yield while reducing costs.

Introducing plant enzymes into yeast for compound synthesis

Producing plant-based compounds in yeast requires specific plant enzymes. The enzyme critical for synthesizing artepillin C was recently identified by researchers at Kyoto University, who collaborated with Kobe University to incorporate this enzyme into the yeast Komagataella phaffii. This yeast species is particularly suited for high-density growth and does not produce alcohol, making it ideal for producing complex compounds without inhibiting cell growth.

The Kobe University team adjusted the yeast’s cellular machinery to boost production levels, resulting in artepillin C concentrations that are ten times higher than previously achieved. They achieved this through modifications in the yeast’s metabolic pathways and selective reversal of mutations to allow for higher cell densities in the fermenters.

Next steps to increase yield and efficiency

The research team continues to refine the process, exploring ways to further improve artepillin C yield. One approach involves enhancing the enzyme that catalyzes the final production step or increasing the availability of precursor compounds. Another strategy is developing a method to export artepillin C from the yeast cells into the growth medium. Engineering a transporter molecule capable of selectively moving artepillin C out of the cell while retaining precursor compounds could enhance efficiency and yield.

Potential for microbial production of other plant-derived medicines

The success of this bioengineering approach with artepillin C suggests that the technique could be adapted for a broad range of plant-derived compounds. Thousands of plant metabolites share similar structures with artepillin C, opening possibilities for the microbial production of diverse medicinal compounds.

"There is the very real possibility that the knowledge gained from the production of artepillin C can be applied to the microbial production of other plant-derived compounds.”

Dr. Hasunuma Tomohisa

Reference: Bamba T, Munakata R, Ushiro Y, et al. De novo production of the bioactive phenylpropanoid Artepillin C using membrane-bound prenyltransferase in Komagataella phaffii. ACS Synth Biol. 2024. doi: 10.1021/acssynbio.4c00472

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