Marine bacterial enzyme HapC reveals new possibilities for bioactive compound synthesis

A research team from Taipei Medical University has discovered a new enzyme, HapC, from the marine bacterium Hahella chejuensis, which opens a novel pathway for synthesizing bioactive compounds. Published on July 6, 2026, in The FEBS Journal, this study led by Professor Andrew H.-J. Wang highlights HapC's flexibility in producing non-native prodiginines, compounds known for their medicinal properties.

Understanding the Role of HapC in Biosynthesis

The enzyme HapC plays a crucial role in the final step of biosynthesizing prodiginines, including the well-known compound prodigiosin. This pigment is significant due to its antibacterial, anticancer, and antifungal properties. Researchers aimed to explore how flexible this enzyme could be in creating new variants of prodiginines.

By utilizing modified short-chain chemical building blocks, the TMU team successfully produced six new prodiginine compounds in laboratory settings. Notably, two of these compounds—3,4-dimethyl-6-methoxyprodiginine and 2-ethyl-6-methoxyprodiginine—had not been synthesized by any known prodigiosin-forming enzymes before, showcasing HapC's unique catalytic abilities.

Investigating HapC's Mechanism of Action

To better understand how HapC functions, the research team constructed a structural model and performed docking simulations to analyze its interactions with ATP and prodiginine products. Wang stated, "We wanted to understand how nature builds these red-pigment molecules, not only by looking at the final product but by following the enzyme's working steps." This approach revealed a three-phase catalytic cycle involving ATP binding, substrate positioning, and product release.

The findings indicate that HapC operates like a molecular assembly station, activating reactions and guiding the joining of chemical building blocks. This insight into the enzyme's active sites and catalytic cycle paves the way for further exploration of its potential in natural product discovery.

Future Implications of HapC in Compound Libraries

The newly synthesized prodiginine analogs are not currently being proposed as medicinal products, but they provide valuable options for researchers to test and compare their biological activities. The study suggests that with a clearer understanding of HapC, scientists can investigate whether it can be engineered to accept additional building blocks, thereby expanding the libraries of compounds available for research.

The next steps involve assessing the biological activity of these new analogs and determining the potential of HapC as a tool for advancing discoveries in medicine, biotechnology, and agricultural biocontrol.