Polymer Biochemistry
Life is based on polymers. Of course, the most well-known example is DNA, because nowadays every child knows that DNA contains genes that form the code of life. DNA, like RNA, is a long unbranched polymer made of nucleotides. This information is used to produce a different type of polymers, the proteins. Also these polymers are unbranched chains, but consist of amino acids. These chains have the amazing capability to fold into specific three-dimensional structures, which enable them to act as little molecular machines.
However, as important as these two polymers are, a third class of polymers is usually less considered but at least equally important: polymers made of sugar. The most prominent example is the substance, which provides half the caloric uptake of humankind: starch. In contrast to the examples above, starch possesses a complex branched structure, but contains only a single type of monomer, namely the sugar glucose. Glycans, as the sugar-based polymers are called, play central roles in many aspects of life. Energy storage is certainly the most dominant role if measured by mass, but glycans are also knwon to be involved in cell-cell signalling processes, they are central components of cell walls giving for example trees the stability they need to grow over 100m, they even play a role in immune defense.
The formation and the degradation of polymers, in particular branched polymers such as glycans, is a complex process involving a large number of enzymes. Some glycans, such as starch, are insoluble, so synthesis and degradation processes take place on a complex surface - and not in solution, as is usually considered when investigating biochemical processes in isolation. Moreover, many enzymes involved in glycan metabolism, perform a certain well-defined reaction pattern, but they are extremely felxible when it comes to the exact nature of their substrates. Often, enzymes just recognise a certain end of a polymer but do not care how the rest looks like. This leads to the complication that such an enzyme can catalyse an enormous number of distinct chemical reactions.
All these issues make it very complicated to find consistent and unifying descriptions for the enzymes acting on polymers. In our research, we aim at developing new theoretical concepts, which allow us to understand the action of these enzymes. With such an understanding, we hope to be able to control polymer synthesis and degradation processes with such a precision that we can design tailored polymers for specific purposes.
We are currently involved in four different projects on polymer biochemistry, each of them is part of a collaborative consortium that includes experimental teams. We develop mathematical and numerical approaches to tackle precise scientific questions with methods and tools complementary to those of our collaborators.
The project DesignStarch, funded under the ERA-CAPS scheme by the DFG, the BBSRC (UK) and the SNF (CH) is getting to an end. For three years we have applied theoretical and synthetic approaches to reconstruct the process of starch synthesis in yeast, an organism that usually does not produce starch.
The project CornWall, funded by the BMBF has recently been extended. Here we face the industrial challenge to convert agricultural residues from crops into valuable chemicals. Plant cell wall is made of several polymers, including abundant quantities of sugar based polymers called cellulose and hemicellulose. We focus on the extraction and degradation of those, which is central in the industrial conversion process, and yet, so far, limiting.
We are also part of a Marie Skłodowska-Curie Initial Training Network funded by the European Commission, which granted two distinct PhD projects in our laboratory. The PoLiMeR consortium investigates the metabolism and regulation of polymers in the liver (glycogen and lipids). By collecting data and building models we aim at understanding the common fundamental principles that may explain rare and specific metabolic diseases.
Contact: Dr. Adélaïde Raguin, Yvan Rousset, Chilperic Armel Foko Kuate, Prof. Dr. Oliver Ebenhöh
Key Publications
- Kartal, Ö., & Ebenhöh, O. (2013). A generic rate law for surface-active enzymes. FEBS letters, 587(17), 2882-2890.
- Kartal, Ö., Mahlow, S., Skupin, A., & Ebenhöh, O. (2011). Carbohydrate‐active enzymes exemplify entropic principles in metabolism. Molecular systems biology, 7(1), 542.
- Prats, C., Graham, T. E., & Shearer, J. (2018). The dynamic life of the glycogen granule. Journal of Biological Chemistry, 293(19), 7089-7098.
- Raguin, A., & Ebenhöh, O. (2017). Design starch: stochastic modeling of starch granule biogenesis. Biochemical Society Transactions, 45(4), 885-893.
- Foster, C. E., Martin, T. M., & Pauly, M. (2010). Comprehensive compositional analysis of plant cell walls (lignocellulosic biomass) part II: carbohydrates. JoVE (Journal of Visualized Experiments), (37), e1837.
- van Eunen, K., Simons, S. M., Gerding, A., Bleeker, A., den Besten, G., Touw, C. M., ... & Bakker, B. M. (2013). Biochemical competition makes fatty-acid β-oxidation vulnerable to substrate overload. PLoS Comput Biol, 9(8), e1003186.
- Pfister, B., Zeeman, S. C., Rugen, M. D., Field, R. A., Ebenhöh, O., & Raguin, A. (2020). Theoretical and experimental approaches to understand the biosynthesis of starch granules in a physiological context. Photosynthesis Research, 1-16.
Further reading