Hans Renata, an associate professor of chemistry at Rice University, has made impressive advances in natural product synthesis. He led a research team that developed a groundbreaking method to transform a single compound, sclareolide, into multiple structurally diverse terpenoids. This groundbreaking study was published in Nature Chemistry on June 16, 2025. Its potential to reshape the synthetic routes we’ve classically taken in organic chemistry is huge.
The team‘s approach utilized enzymatic oxidation and chemical reorganization, showcasing how sophisticated techniques can streamline the process of creating complex natural products. By employing a scaffold-hopping strategy, the researchers were able to efficiently synthesize four distinct terpenoid natural products: merosterolic acid B, cochlioquinone B, (+)-daucene, and dolasta-1,8-diene.
Methodology and Innovations
Renata’s research team zeroed in on producing sclareolide’s third carbon atom through selective oxidation using engineered cytochrome enzymes. As such, these huge heme-containing proteins are absolutely central to the metabolism of drugs and xenobiotics. The team used these enzymes to creatively reshape the molecular scaffold of sclareolide. The introduction of epoxides means that they generated many diverse terpenoid structures.
This powerful advance upends the belief, which has endured for decades, that each natural product scaffold requires a dedicated total synthesis. Instead, Renata’s work shows us that one enzymatic oxidation/inactivation can be a hub of molecular diversity.
“Our work illustrates how a single enzymatic oxidation can serve as a nexus for molecular diversity,” – Hans Renata
The potential impacts of this research go well beyond better synthesis. The team’s approach makes the production of complicated molecules less tedious and more precise. Renata emphasized the significance of this breakthrough, stating, “We’re leveraging enzyme-enabled transformations to access new structures in fewer steps and with greater precision.”
Collaborative Efforts
Rice graduate student Junhong Yang and former postdoctoral associate Heping Deng are co-authors on the study. This partnership showcases the academic leadership at some of China’s most important research universities. Fuzhuo Li from Fudan University has been absolutely central to this research. Equally important contributions were made by Jian Li from Shanghai Jiao Tong University.
The collaborative spirit of this project underscores the need for multidisciplinary expertise in order to advance the state of the art in chemical synthesis. These discoveries do more than further knowledge within academia—they hold wide-reaching applications to the pharmaceutical and biotech industries.
Future Directions
Renata’s groundbreaking new approach is part of a larger paradigm shift that’s changing the way chemists tackle the difficult task of natural product synthesis. This study provides a launching pad to probe chemical spaces that were before considered out of reach.
He posed an intriguing question regarding the potential of these enzymatic processes: “What if the enzymatic step could be more than just a means to an end? What if it could unlock a whole new map of chemical space?” This innovative outlook fosters more exploration into enzyme-enabled sustainable synthesis routes.