The team achieved a breakthrough in the production of doxorubicin
An international team of researchers has achieved a breakthrough in the production of doxorubicin, a critical chemotherapy agent. The study finds and resolves molecular ‘bottlenecks’ that have limited the natural production of this drug for over 50 years.
Doxorubicin is a chemotherapy drug, first approved for medical use in the 1970s, and has since become a cornerstone in treating various cancers such as breast cancer, bladder cancer, lymphomas, and carcinomas. However, bacteria naturally produce this drug very inefficiently, and so the pharmaceutical industry has relied on expensive, multi-step semi-synthetic processes.
Researcher Keith Yamada from the University of Turku, Finland, and a lead scientist on the study, said, “We have uncovered several independent factors that limit the formation of doxorubicin. By addressing these bottlenecks, we have harnessed rational strain engineering to pave the way for cost-effective manufacturing that can meet growing global demand.”
The study was the result of an international collaboration involving six research laboratories: the University of Turku in Finland, three laboratories in the US, and two in Leiden, the Netherlands. Together, the teams identified three constraints that prevent high-yield production of doxorubicin.
Firstly, the specific natural ‘biological power supply’ redox partners named Fdx4 and FdR3 were identified, which provide the necessary electron flow to power the drug-producing enzyme.
Secondly, they found that a protein called DnrV acts as a drug-binding ‘molecular sponge’ that sequesters doxorubicin, preventing it from shutting down the enzyme’s own production machinery.
Lastly, using X-ray crystallography, the team visualised the enzyme for the first time, revealing that the drug molecule sits in an unfavourable position within the enzyme, which explains the slow reaction rate.
Combining these discoveries enabled the researchers to engineer a new strain of bacteria that produces 180% more doxorubicin than current industrial standards.
To bring these findings to the real world, the company Meta-Cells Oy was formed at the University of Turku, aiming to commercialise these advanced technologies for the sustainable manufacturing of essential antibodies and anti-cancer agents. This shift toward fully biosynthetic production promises a cleaner, more reliable supply of life-saving medicines.
The study was published in the journal Nature Communications.
