Some of the most complicated chemical structures in medicine can take chemists many carefully controlled steps to produce. Yet, inside bacteria, specialised enzymes can assemble similarly intricate molecules in a single sequence of reactions. Now, scientists have captured a near-atomic image of one such enzyme, revealing how it helps construct the molecular framework associated with an important cancer drug. The research team, involving scientists from the University of Tokyo and Tohoku University in Japan, visualised an enzyme called SacC. It plays a central role in producing safracin B, a bacterial compound whose complex five-ring structure is also found in trabectedin, a drug used to treat soft-tissue sarcoma. The findings were published in the Journal of the American Chemical Society in October 2026.
Trabectedin is an anticancer drug that acts by interacting with DNA, interfering with processes involved in cancer cell growth. Its intricate molecular structure makes it particularly challenging to synthesise chemically. They focused on how bacteria construct a related molecular framework naturally. SacC carries out a remarkable seven-step catalytic sequence, forming two new carbon-to-carbon bonds and assembling a five-ring core structure. Think of the enzyme as a microscopic production line. An unfinished molecule moves through different reaction stages as parts of the enzyme change their positions to carry out each chemical transformation. What makes this process remarkable is that the enzyme performs these reactions in water, at room temperature, with considerable precision. Understanding how SacC manages this complicated chemistry could eventually help scientists reproduce or modify similar reactions to develop useful compounds.
Why was the enzyme so difficult to photograph?
Capturing SacC’s structure was not straightforward. Its different sections move considerably during the reaction, meaning that individual enzyme molecules can be caught in different shapes when frozen. Combining images of these varying structures can produce a blurred result. The enzyme also tended to clump together in solution, making it difficult to prepare suitable samples for imaging. The breakthrough came from two complementary approaches. First, they designed small synthetic molecules that mimic intermediate compounds formed during the enzyme’s reaction. These probes helped trap SacC at a particular stage of its catalytic cycle. Second, they identified a small partner protein called SacE, which stabilised SacC and prevented it from aggregating. With the enzyme sufficiently stable, the team rapidly froze the samples in a thin layer of ice and examined them using cryo-electron microscopy (cryo-EM). By reconstructing thousands of individual images, researchers obtained a three-dimensional structure detailed enough to reveal molecular features at near-atomic resolution.
What could this mean for future cancer drugs? The images captured an early stage of the enzyme’s activity, when its molecular building block had just been loaded. The later stages, including the formation of the complete ring structure and release of the finished product, have not yet been visualised in comparable detail. They hope to capture these additional stages and investigate whether similar methods can be applied to other enzymes that produce medically useful compounds. This discovery does not introduce a new cancer treatment or immediately make trabectedin easier to manufacture. Instead, it provides a valuable structural starting point for understanding how nature builds complex molecules. By learning from these biological assembly lines, scientists may eventually find new ways to design, improve or produce compounds with therapeutic potential.
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