Scientists Unlock Breakthrough Enzyme to Redesign Cancer and HIV Drugs
Scientists have developed a new method to modify complex plant-based compounds called pentacyclic triterpenoids (PTs). These molecules hold promise for treating diseases like cancer and HIV but are notoriously difficult to alter in the lab. A research team led by Zhang, Chen, Wang, and collaborators has now uncovered an enzyme, ApPT, that can precisely tweak these compounds in ways previously thought impossible.
The breakthrough combines bioinformatics, molecular biology, and green chemistry to create a more efficient and sustainable approach to drug development. Pentacyclic triterpenoids, found in plants, are known for their therapeutic potential. Drugs like maslinic acid, oleanolic acid, and betulinic acid—currently in clinical trials for cancer, HIV, and inflammation—rely on these structures. However, their complex shapes make chemical modifications slow, expensive, and often ineffective.
The team identified a bacterial enzyme, ApPT, capable of targeting specific carbon-hydrogen bonds in PTs with high precision. Unlike traditional methods, this enzyme works selectively, preserving the core medicinal properties of the molecules while allowing fine-tuned adjustments. Its ability to add functional groups at aliphatic sites—areas once considered off-limits—opens new possibilities for improving drug solubility, stability, and effectiveness.
The researchers paired computational bioinformatics with lab experiments to uncover ApPT's potential. By screening bacterial P450 enzymes, they found one that not only recognised a wide range of PTs but also maintained strict control over the modification process. This selectivity means scientists can now generate diverse drug candidates without losing the original compound's beneficial effects.
Beyond its immediate applications, the platform offers a greener alternative to conventional synthesis. It reduces reliance on harsh chemicals and energy-intensive processes, aligning with modern sustainability goals. The team's approach also provides a blueprint for discovering similar enzymes that could unlock modifications in other natural products. The discovery of ApPT and its chemo-enzymatic platform allows for the creation of PT derivatives that were previously unattainable. This method enhances the pharmacokinetic properties of drug candidates, making them more effective and easier to develop. With broader applications in drug discovery, the research marks a step forward in both medicinal chemistry and sustainable science.
