Unit B: Coupled biocatalytic reactions

Our Challenge

We aim at understanding natural catalysts, namely enzymes. Enzymes in cells are able to perform complex coupled catalytic processes. These function effectively, maybe more efficiently than in artificial human-engineered catalysts. Biocatalytic processes ‘only’ need to be deciphered or recombined in alternative ways. This is our challenge!

With this knowledge, we'd like to design of smart catalysts. For example, we wish to engineer electron transfer chains.

Our approach

Our efforts are first directed to understanding in detail natural enzymes. We focus on the catalytic mechanisms and dynamics of  biocatalysts capable of controlling coupled biocatalytic reactions. Our key questions are:

  • How are two catalytic reactions coordinated at a single active site?
  • How does the interaction between active sites work in enzymes? Here, for instance, we are interested in substrate channeling, sequestering of reactive intermediates and servicing between active sites.
  • How is the electron transfer between enzymes controlled?
  • How can we design catalytic systems learning from nature?

Our studies strive to elucidate the molecular bases of various aspects of catalytic multi-functionality.

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.

Team

Robert Bittl
(Pulsed) EPR spectroscopy

Nediljko Budisa
Protein modification by non-natural amino acids

Holger Dau
X-ray spectroscopy, QCL-IR/FTIR

Holger Dobbek
Enzymology, X-ray crystallography, Fe/S-enzymes

Matthias Driess
Molecular (heterobimetallic) active site mimics

Peter Hildebrandt
Raman spectroscopy (surface-sensitive, in situ)

Silke Leimkühler
Molecular enzymology, molybdoenzymes

Oliver Lenz
Biochemistry, enzyme engineering, hydrogenases

Christian Limberg
Model compounds, O2- and CO2-activation

Maria Andrea Mroginski
Theory (QM/MM, MD)

Henrike Müller-Werkmeister
(transient) 2D-IR & ultrafast UV-Vis spectroscopy

Peter Neubauer
Bioprocess engineering, enzyme overproduction

Kallol Ray
Bioinorganic chemistry, O2 activation

Patrick Scheerer
X-ray crystallography, XFEL

 

Christian Spahn
Cryo electron microscopy

 

Roderich Süssmuth
Biochemistry, analytics, lanthipeptide synthetases

Petra Wendler
Cryo electron microscopy

 

Ulla Wollenberger
Protein electrochemistry

 

Ingo Zebger
IR spectroscopy (surface-sensitive, in situ)

Athina Zouni
Biochemistry, X-ray crystallography, XFEL

Contact Unit B

Prof. Dr. Holger Dobbek
HU Berlin
Department of Biology
Philippstraße 13
10115 Berlin
+49 (0)30 2093-6369
holger.dobbek(at)biologie.hu-berlin.de

Prof. Dr. Silke Leimkühler
U Potsdam
Department of Biology and Biochemistry
Karl-Liebknecht-Straße 24–25
14476 Potsdam-Golm
+49 (0)331 977-5603
sleim(at)uni-potsdam.de