Bioengineered E. coli bacteria can now produce rhododendron-derived drugs, offering a promising avenue for the synthesis of compounds with anticancer, anti-HIV, antidiabetic, and anti-inflammatory activities. This groundbreaking achievement by Kobe University researchers is the result of a rational design strategy that has created a platform for the industrial production of drug candidates. The team, led by bioengineer HASUNUMA Tomohisa, has successfully engineered E. coli to produce orsellinic acid, a core compound derived from rhododendron species with remarkable pharmacological properties. This achievement marks a significant advancement, as previous attempts at microbial production of orsellinic acid had yielded disappointingly low results. The Kobe University team's success in producing orsellinic acid in E. coli is a testament to the potential of bioengineering in overcoming supply issues in natural products research. The team's rational design strategy involves introducing appropriate genes from plants, fungi, and bacteria, analyzing the organism's metabolism, and optimizing culture conditions. This approach has led to a 40-fold improvement in production, achieving 202 mg of orsellinic acid per liter. The team also introduced a further gene from rhododendron, completing the biosynthesis of a pharmacologically relevant compound, grifolic acid, known for its potent anticancer and analgesic properties. While the yield of grifolic acid was low, the team acknowledges the need for further optimization of the production process and has already identified potential bottlenecks for future studies. The broader implications of this research extend beyond the production of specific compounds. HASUNUMA Tomohisa explains that the rational design strategy employed in this study serves as a foundational technology for the production of various complex compounds using E. coli. This achievement was made possible through funding from the Japan Society for the Promotion of Science (Program for Forming Japan's Peak Research Universities (J-PEAKS)) and the Japan Science and Technology Agency (grant JPMJGX23B4), and was conducted in collaboration with researchers from the University of Minho and the RIKEN Center for Sustainable Resource Science. The study's findings have been published in the journal Metabolic Engineering, offering a promising avenue for the development of new drugs and therapies.
