Researchers aim to convert the plentiful natural resource of wood into practical materials, relying on a molecular machine that exists in fungi to break down the complex structure into simpler components. A team led by a researcher from Kobe University has developed a test feed for this fungal molecular machine, allowing them to monitor its action in a way that’s close to its natural state, which paves the way for enhancements and potential industrial applications.
Researchers aim to convert the plentiful natural resource of wood into practical materials, relying on a molecular machine found in fungi that breaks down the complex structure into simpler components. A team led by a Kobe University researcher has created a test feed for this fungal molecular machine, enabling them to observe its operation in a manner close to its natural function. This development opens the door for improvements and potential industrial applications.
Biochemical engineers are focused on transforming the renewable resource of wood into various products such as bioplastics, medical chemicals, food additives, or fuels. However, the intricate structure of wood has posed significant challenges. Bioengineer KOH Sangho from Kobe University explains, “Wood consists of various chemically linked materials like lignin and hemicellulose, which must first be separated to be used as source materials.” Essentially, wood needs to be stripped down. Fungi possess enzymes—tiny chemical machines—that can perform this function. However, to enhance and adapt these enzymes for industrial purposes, a deeper understanding of their mechanisms is necessary. Unfortunately, researchers previously lacked a suitable “substrate” for studying these enzymes. Koh recalls, “As a graduate student at Shinshu University, I struggled to generate the typical enzymatic reaction dynamics graphs we’re familiar with from textbooks using commonly used test substrates. I even contacted the original researcher who discovered the enzyme to understand what I was doing wrong. He assured me that my results were typical for those attempting to characterize this enzyme.”
Driven by this challenge, Koh and his team developed a novel material that preserved the essential structural characteristics of the enzyme’s natural substrate while being simple enough for chemical modification and computational modeling. “Our ability to create a suitable substrate stemmed from previously identifying another enzyme that allowed us to produce very specific hemicellulose fragments that couldn’t be generated otherwise. Only with these fragments could we chemically synthesize a fitting test substrate,” Koh explains, highlighting why previous attempts had failed to characterize the enzyme effectively.
The bioengineers recently published their findings in the journal Biochemical and Biophysical Research Communications. As the first team to observe the isolated enzyme’s behavior in a nearly natural environment, they successfully determined its reaction speed and affinity—critical metrics for bioengineers focused on enzyme development. Koh reflects, “When I finally saw the textbook-like reaction dynamics emerge from my designed substrate, it was a joyous moment. Now, we can accurately characterize the enzyme’s ‘true’ nature and enhance its industrial application.”
Their computational simulations revealed the key differences between their method and previous approaches. Previous researchers had concentrated solely on the specific site within the substrate designated for cleavage, leading to test substrates that mostly featured the connecting structure. Conversely, Koh’s newly synthesized substrate includes a short hemicellulose tail attached to the reaction site, which is critical as it is this tail that the enzyme binds to when it performs its function.
Now equipped with clear performance metrics and insights into the enzyme’s reaction mechanism, the researchers plan to explore better alternatives within different fungi and experiment with chemical modifications to assess their impact on enzyme performance. Furthermore, they believe that their test substrate will aid in understanding how this enzyme collaborates with others to break down various wood components. Koh concludes, “We believe this marks a significant advance toward applying this process industrially to generate useful chemicals from this abundant natural resource.”
This research was supported by the Japan Society for the Promotion of Science (grants 23K13870 and 17K07874) and the Sugiyama Sangyou Kagaku Research Foundation. It was conducted at Shinshu University in collaboration with researchers from the National Institute of Advanced Industrial Science and Technology, Kobe University, and Shinshu University.
