Scientists At Warwick University Crack Bacteria’s Anti-Cancer Code

Photo Credit: Pixabay / M. Richter

(UNITED KINGDOM) –  Researchers at Warwick University have discovered how certain bacteria naturally make different versions of anti-cancer molecules. While it isn’t a cure for cancer, the discovery is considered groundbreaking. Scientists were aware that some bacteria already naturally produce anti-cancer chemicals; one such strain became a potent drug for treating those with T-Cell Lymphoma. The drug, Romidepsin, is created using anti-cancer molecules from the Chromobacterium violaceum bacterium. The bacteria produce FR-901375, a natural molecule in the medication family known as HDAC inhibitors.

What scientists didn’t understand was how the bacteria naturally assembled the proteins to create the beneficial medication. Using several methods, researchers have isolated a major piece of the puzzle - docking domains. Docking domains are tiny protein regions that allow enzymes to connect to multiple compatible partners, instead of all of them permanently connecting to one.

So, how did they crack the code?

The scientists pored over bacterial DNA databases to locate the genes responsible for creating the beneficial anti-cancer medication. Once they had the information, they were able to grow the bacteria and confirm that it produced the appropriate chemicals. Then they extracted and isolated the enzymes to study how they would interact. Next, the team used AlphaFold to predict how proteins fit together prior to experimental testing.

AlphaFold is a Google DeepMind AI system used to predict the 3D structure of proteins by the sequence of their amino acids. In the fourteenth Critical Assessment of protein Structure Prediction (CASP14), AlphaFold was ranked as the top protein structure prediction method. CASP14 noted that AlphaFold produced predictions with a high level of accuracy.

Once they found the missing piece, scientists mutated the proteins by deliberately changing the docking regions. When they broke the docking domain, the bacteria could no longer produce the molecules needed for cancer treatment drugs. The discovery provided strong support for the assessment that the docking domains in those bacteria were essential to producing the anti-cancer molecules.

Photo Credit: Pixabay / Qimono

"For decades, we've known that bacteria can naturally produce multiple versions of powerful anti-cancer drugs, yet we had no idea how they achieved this," said Research Fellow for the Department of Chemistry at the University of Warwick, Dr. Munro Passmore, "This work finally cracks that code. We've identified how the different enzymes communicate and cooperate to produce these drug variants.”

This is something Passmore says has been unknown to researchers because the system is, as he puts it, “elegantly economical.” He further implies that the breakthrough is necessary for scientists to engineer anti-cancer drugs more naturally.

Drugs made by bacteria are difficult to produce; while chemists can make them in labs, it’s costly and complicated. With the recent discovery, scientists hope to use nature's code to produce more of these essential medications at an accelerated speed. That means it may be possible to improve existing drugs, tailor drugs to different cancers, and develop drugs with less toxicity.

To add to or correct any information in this report, please contact me at kristin.h@lead4earth.org.