Kobe Bioengineers Revolutionize Drug Candidate Production with E. coli
Kobe University bioengineers have developed a platform using bioengineered E. coli bacteria to produce compounds with potential anticancer, anti-HIV, antidiabetic, and anti-inflammatory activities. This achievement aims to enable industrial production of drug candidates.
Plants naturally produce pharmacologically active substances, such as orsellinic acid-derived meroterpenoids found in Rhododendron species. However, relying on natural sources often proves unreliable and expensive for large-scale production. Previous microbial production attempts for orsellinic acid, a crucial precursor, have consistently resulted in low yields.
Doctoral student Tomita Itsuki noted that supply issues frequently hinder the advancement of promising natural products in research.
A Novel Strategy for Industrial-Scale Production
The research team, led by bioengineer Hasunuma Tomohisa, specializes in the rational design of microorganisms like Escherichia coli. Their innovative strategy involved introducing appropriate genes from plants, fungi, and bacteria, meticulously analyzing the organism's metabolism, and optimizing culture conditions to establish an industrial-scale production platform using E. coli.
Breakthrough in Orsellinic Acid Production
The team's findings, published in Metabolic Engineering, mark a significant milestone.
Published in Metabolic Engineering, the team reported producing 202 mg of orsellinic acid per liter.
This represents a 40-fold improvement over previously reported microbial production levels and marks the first successful production of the core compound in E. coli. Tomita underscored this as a significant accomplishment in recreating a complex eukaryotic biosynthetic pathway within the bacterium E. coli.
Expanding the Platform: Grifolic Acid and Beyond
In an additional application, the group introduced a Rhododendron gene to complete the biosynthesis of grifolic acid, a compound renowned for its anticancer and analgesic properties. While the engineered bacteria successfully produced the target compound, the initial yield was low. Hasunuma's team acknowledged the need for further optimization of the production process, having already identified potential bottlenecks for future studies.
Hasunuma indicated that the established platform can be immediately applied to the production and evaluation of related compounds and their derivatives.
He also emphasized that the rational design strategy serves as a foundational technology for producing various complex compounds using E. coli.
Funding and Collaboration
This groundbreaking research was funded by 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). It involved collaboration with researchers from the University of Minho and the RIKEN Center for Sustainable Resource Science.