Herbal medicine is challenging to manufacture on a large scale. However, a team of bioengineers from Kobe University has successfully altered the cellular processes in a type of yeast, enabling the production of a specific molecule in fermenters at record levels. This breakthrough also opens the door to producing various other plant-based compounds with microbes.
Herbal medicine is challenging to manufacture on a large scale. A team of bioengineers from Kobe University has successfully altered the cellular processes in a type of yeast, enabling the production of a specific molecule in fermenters at record levels. This breakthrough also opens the door to producing various other plant-based compounds with microbes.
Herbal products can provide numerous health benefits, yet they often don’t lend themselves to mass production. Take artepillin C, for instance, which possesses antimicrobial, anti-inflammatory, antioxidant, and anticancer properties but is only obtainable from bee culture products. Bioengineer HASUNUMA Tomohisa from Kobe University states, “To achieve a high-yield, cost-effective supply, it is advantageous to produce it using bioengineered microorganisms that thrive in fermenters.” However, this goal presents its own technical hurdles.
The first step involves identifying the enzyme, which is essentially the molecular machinery, that the plant employs to create a specific product. “The plant enzyme crucial for producing artepillin C was only recently identified by YAZAKI Kazufumi at Kyoto University. He inquired if we could harness it for production in microorganisms given our expertise in microbial production,” shares Hasunuma. The team then attempted to insert the gene that encodes the enzyme into the yeast Komagataella phaffii. This yeast is preferable over brewer’s yeast as it can generate higher densities of desired compounds without producing alcohol, which can hinder cell growth.
The findings, published in the journal ACS Synthetic Biology, reveal that their engineered yeast produced ten times more artepillin C than was previously possible. This was achieved by meticulously fine-tuning crucial stages of the artepillin C production process. Hasunuma notes, “Interestingly, artepillin C does not easily exit the cell and tends to build up inside it. Thus, we needed to cultivate the yeast cells to high densities in our fermenters by eliminating certain mutations that hindered the organism’s growth.”
Hasunuma already has ideas for further enhancing production. One strategy could involve increasing the efficiency of the final and essential chemical step by modifying the necessary enzyme or amplifying the supply of precursor chemicals. Another potential approach is to develop a method for transporting artepillin C outside of the cell. “If we can alter a transporter— a molecular structure that moves chemicals into and out of cells—to export the product while retaining the precursors inside, we could achieve even greater yields,” says Hasunuma.
However, the implications of this research extend beyond just this compound. Hasunuma elaborates, “Given that there are thousands of naturally occurring compounds with strikingly similar chemical structures, the insights obtained from artepillin C production could likely be utilized for the microbial generation of other plant-derived substances.”
This project received funding from the Japan Society for the Promotion of Science (grant 23H04967), the RIKEN Cluster for Science, Technology and Innovation Hub, and the Japan Science and Technology Agency (grant JPMJGX23B4). The research was carried out in collaboration with scholars from Kyoto University and the RIKEN Center for Sustainable Resource Science.
