Understanding bacteria’s role in transforming steroids to pharmaceuticals

For decades, pharmaceutical companies have been using bacteria found in soil and water to chemically convert steroids into effective treatments for human diseases. One example is cortisol, which is used to treat asthma and skin rashes. But how bacteria convert steroids is not fully understood.

Now a research team from the University of Guelph has taken a significant step forward in answering that question. Using the Canadian Light Source (CLS) at the University of Saskatchewan, Dr. Stephen Seah and colleagues have determined the 3D structures of steroid-transforming enzymes from Proteobacteria (also called Pseudomonadota), a large, diverse family of gram-negative bacteria named after Proteus – the shape-shifting Greek sea god.

Studying the 3D structure of these enzymes, which Seah says would be impossible without the ultrabright X-ray source of the CLS, is key to understanding how this Proteobacteria chemically transforms steroids – such as bile acids – which are typically resistant to being changed.

Seah and his colleagues found that the bacteria have evolved to transform steroids as a means to obtain carbon and energy for their own growth. However, he says, these transformations can be harnessed to chemically alter steroids into compounds that we can use for disease treatments; a discovery that will help advance future pharmaceutical development.

“If we understand the process, we can manipulate other bacteria to produce novel compounds that may have medicinal properties,” says Seah. “I think my work helps fill in this gap of knowledge.” The team’s research findings were published recently in both the Journal of Biological Chemistry and Biochemistry.

This new research, says Seah, also opens the door to exploring the potential of other enzymes in bacteria to change the chemical structure of steroids. “In other words, one could create steroids with diverse chemical structures using the many steroid-modifying enzymes that bacteria produced to alter naturally occurring steroids,” he says. “Some of these modified steroids may have therapeutic properties.”

Besides their potential application in pharmaceutical production, bacteria transformation of steroids such as bile acids can also have a more direct impact on human health.  Bile acids are synthesized in the human liver and secreted into our intestine to “help us digest fat,” but bacteria in the gut can chemically change these bile acids and “affect human health either negatively or positively,” says Seah.   Gall stones, for example, can result from bacteria interacting with bile acids. “In my lab, we’re trying to understand these processes”

“There are many unknowns so there are a lot of new things to discover.”

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Rolfe, Nicolas, Dustin Myskiw, Matthew T. Patton, Taylor JB Forrester, Matthew S. Kimber, and Stephen YK Seah. "Sad from Proteobacteria is a Structurally Distinct ALDH3 Enzyme Specialized for the Oxidation of Steroidal Aldehydes." Biochemistry 64, no. 17 (2025): 3735-3744. https://doi.org/10.1021/acs.biochem.5c00213 

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To arrange an interview with the researcher, contact:

Greg Basky
Communications Coordinator
Canadian Light Source
306-370-9446
greg.basky@lightsource.ca