In recent years, researchers have taken impressive steps to improve the versatility of alcohol dehydrogenase (ADH) enzymes. Collectively, these breakthroughs shed light on the enzymes’ promise for industrial applications in synthesizing amides and thioesters. It was the pioneering research of Matteo Damian and his team at Monash University. They showed that taking advantage of the ‘hidden reactivity’ of ADHs can enable the green production of important building blocks for pharmaceuticals, natural products and high-tech materials. Related work by the same researchers recently appeared in Angewandte Chemie International Edition. I downloaded the article today, 8 October 2025 and on phys.org, it jumps to the DOI 10.1002/anie.202515469.
This publication describes an interesting new oxidative coupling process that can be carried out using ADHs. This process is particularly exciting as it can lead to high purity yields of 99%+. It does so with a truly incredible enzyme load of just 0.1 mol% of the enzyme compared to the alcohol substrate. This remarkable efficiency represents a notable breakthrough for enzymatic reactions, making ADHs powerful catalysts in chemical production.
Industrial Relevance of Amides and Thioesters
Amides and thioesters are substrates with significant applications in pharmaceuticals and materials science. These compounds are the basis for discovering new medicines and natural products, which are becoming more and more important around the world. That’s why industries are looking so hard for smarter, more sustainable ways of producing goods. The clean synthesis capabilities of ADHs offer a potentially powerful alternative to more traditional chemical approaches that often lead to hazardous byproducts.
The work demonstrates the tremendous value of ADHs as powerful catalysts for the oxidative coupling of alcohols with amines or thiols. This enzyme mediated process leads to amides and thioester formation. This increasing interest in green chemistry is spurring on innovation. By employing biocatalysts such as ADH, we can prevent potential harm to the environment without compromising yield and efficiency in the production of chemicals.
Exploiting Hidden Reactivity
The concept of ‘hidden reactivity’ describes the unrealized potential of ADHs. By building on these industry capabilities, we can accelerate the invention of new synthetic pathways. His research found that almost half of the candidate examples exhibited novel oxidative coupling reactions. This really shows the breadth of function these enzymes have! By pinpointing this secret potential and tapping into it, scientists will be able to unlock better methods of synthesizing complex organic molecules.
Damian et al. carefully assessed several ADHs to determine the breadth of their oxidative coupling activities in an effort to build a clear picture of what they can do. These discoveries significantly broaden our knowledge of how these enzymes work. They provide exciting new opportunities for future research to improve enzymatic reactions for new industrial applications.
Future Implications and Research Directions
The importance of this research goes far beyond the ivory tower—that’s where the real promise lies in transforming how industries such as manufacturing, transportation, and logistics operate. With inflation and economic pressures dominating headlines, companies are focusing on sustainability as a driver for efficiency. Innovating industrial applications ADH-mediated processes have the potential to revolutionize industrial production of amides and thioesters.
We will continue with intensive research in the future towards further maximization of reaction conditions. Another area scientists will investigate is what other substrates these enzymes can break down. Further, research could address how to scale up these reactions for production while focusing on consistency and reliability in yield.