Biology subjects

Frank, O.

Publications and source records attributed to Frank, O..

3 recordsLinked to original sources

bioRxiv2023

Production of 130 diterpenoids by combinatorial biosynthesis in yeast

Diterpenoids form a diverse group of natural products, many of which are or could become pharmaceuticals or industrial chemicals. However, low concentration, presence in complex mixtures and challenging synthesis often limit their exploitation. The modular character of diterpene biosynthesis and the substrate flexibility of the enzymes involved make combinatorial biosynthesis a promising approach. Here, we report on the assembly in yeast of 130 diterpenoids by pairwise combinations of ten diterpene synthases producing (+)-copalyl diphosphate-derived backbones and four cytochrome P450 enzymes (CYPs); 80 of these diterpenoids have not yet been reported. The CYPs accepted the majority of substrates they were given but remained regioselective. Our results bode well for the systematic exploration of diterpenoid chemical space using combinatorial assembly in yeast.

synthetic biology↗

bioRxiv2019

Unraveling nanotopography of cell surface receptors

Cells communicate with their environment via surface receptors, but nanoscopic receptor organization with respect to complex cell surface morphology remains unclear. This is mainly due to a lack of accessible, robust and high-resolution methods. Here, we present an approach for mapping the topography of receptors at the cell surface with nanometer precision. The method involves coating glass coverslips with glycine, which preserves the fine membrane morphology while allowing immobilized cells to be positioned close to the optical surface. We developed an advanced and simplified algorithm for the analysis of single-molecule localization data acquired in a biplane detection scheme. These advancements enable direct and quantitative mapping of protein distribution on ruffled plasma membranes with near isotropic 3D nanometer resolution. As demonstrated successfully for CD4 and CD45 receptors, the described workflow is a straightforward quantitative technique to study molecules and their interactions at the complex surface nanomorphology of differentiated metazoan cells.

cell biology↗

bioRxiv2018

Body size-dependent energy storage causes Kleibers law scaling of the metabolic rate in planarians

Kleibers law, or the [3/4]-power law scaling of the metabolic rate with body mass, is considered one of the few quantitative laws in biology, yet its physiological basis remains unknown. Here, we report Kleibers law scaling in the planarian Schmidtea mediterranea. Its reversible and life history-independent changes in adult body size over 2 orders of magnitude reveal that Kleibers law does not emerge from the size-dependent decrease in cellular metabolic rate, but from a size-dependent increase in mass per cell. Through a combination of experiment and theoretical analysis of the organismal energy balance, we further show that the mass allometry is caused by body size dependent energy storage. Our results reveal the physiological origins of Kleibers law in planarians and thus have general implications for understanding a fundamental scaling law in biology.

biophysics↗