Unit B
Coupled biocatalytic reactions

While the central objective of increasing efficiency and minimizing energy barriers in the respective coupled chemocatalytic processes is already realized in most biocatalytic systems in nature, it ‘only’ needs to be deciphered or recombined in alternative ways.

Thus, our efforts are first directed to understanding in detail natural enzymes, focusing on the catalytic mechanisms and dynamics of multi-functional biocatalysts capable of controlling coupled biocatalytic reactions.

The addressed key questions are how:

• Two catalytic reactions are coordinated at a single active site
• Interfaced catalytic centers allow rapid substrate channeling, sequestering of reactive intermediates, and servicing between active sites
• Complex formation controls electron transfer between enzymes
• These insights can be  employed to realize newly designed catalytic systems.

Thus, our studies strive to elucidate the molecular bases of various aspects of catalytic multi-functionality, thereby inspiring research in all Research Units.

A particularly challenging example are bi- and multifunctional carbon monoxide dehydrogenases, in which the catalytic activities of three coupled metal-containing active sites are coordinated in a way that allows the efficient conversion of CO₂, CoA, and CH₃⁺ into acetyl-CoA. We will analyze how these centers communicate and their different oxidation/catalytic states trigger conformational changes in order to sequester and channel the one-carbon intermediates.

Keeping electrons at a high energy level between separate oxidative and reductive reactions is a widely employed concept in nature to enable biocatalytic processes. This concept will be explored for O₂-tolerant hydrogenases and formate dehydrogenase, and subsequently exploited for coupling these biocatalysts with electron-demanding processes such as CO₂ reduction.

Our Challenge

Smart design of engineered electron transfer chains