Biology subjects

Unger, F.

Publications and source records attributed to Unger, F..

4 recordsLinked to original sources

bioRxiv2025

Valine overproduction with metabolically engineered Methanothermobacter marburgensis

In times of a climate crisis caused by extreme emissions of green-house gases on a global scale, mitigation solutions need to be found. One solution is the system of carbon capture and utilization (CCU), where C1 gases, such as carbon monoxide (CO), carbon dioxide (CO2), or methane, are either redirected from industrial off-gas streams or directly air-captured. A biotechnological process for CCU is the use of Methanothermobacter marburgensis for CO2 fixation and production of value-added compounds. In this study, we focused on valine production, an amino acid important for human or feed stock nutrition. We demonstrated overproduction of valine from CO2 in M. marburgensis with temperature-induced promoters. Here, we reached a 12.9-fold increase in valine production between the OFF- and ON states of the inducible promoter with a maximal specific production rate of 14.17 mg gCDW-1 h-1 of valine in closed batch experiments. In the second approach for valine production, we overexpressed acetolactate synthase genes with resistance to allosteric valine inhibition from Methanothermobacter thermautotrophicus recombinant in M. marburgensis. We identified a strong reduction in allosteric inhibition towards valine. This resulted in specific valine productivity of up to 40 mg gCDW-1 h-1 and states the highest specific productivity on an individual amino acid in methanogens. With those findings, we expanded the toolbox for genetic modification of M. marburgensis by a thermo-inducible promoter system and applied protein engineering for enhanced production of value-added compounds to M. marburgensis. This proof of concept shows the feasibility of archaeal cell factories generation via genetic engineering for industrial production of value-added compounds with thermophilic methanogens.

molecular biology↗

bioRxiv2025

Pilot-scale production of leucine from CO2

On a cellular level, proteinogenic amino acids (AAs) are the building blocks of proteins. On a global scale, AAs serve as important nutrients for humans and animals. Beyond their nutritional value, AAs are of relevance in medicine, and, due to their chemical properties, they are indispensable for applications in many different realms, such as pharmaceutics, cosmetics, animal feed, food, and the beverage industry. Here, we report the first archaeal cell factory for leucine production from CO2 that has been generated by rational design, random mutagenesis and pathway engineering. The cell factory has been bioprocess-technologically examined and successfully scaled-up with regard to productivity, product quality, and operational stability. In a 2-day fed-batch campaign, we produced 181 g of leucine from CO2 at 150 L pilot-plant scale at a mean volumetric leucine productivity of 65 mg L-1 h-1. A thorough techno-economic analysis indicates that the roll-out of leucine production from CO2 is nearly economically feasible on a global scale.

bioengineering↗

bioRxiv2023

Non-synaptic plasticity enables memory-dependent local learning

Synaptic plasticity is essential for memory formation and learning in the brain. In addition, recent results indicate that non-synaptic plasticity processes such as the regulation of neural membrane properties contribute to memory formation, its functional role in memory and learning has however remained elusive. Here, we propose that non-synaptic and synaptic plasticity are both essential components to enable memory-dependent processing in neuronal networks. While the former acts on a fast time scale for rapid information storage, the latter shapes network processing on a slower time scale to harness this memory as a functional component. We analyse this concept in a network model where pyramidal neurons regulate their apical trunk excitability in a Hebbian manner. We find that local synaptic plasticity rules can be derived for this model and show that the interplay between this synaptic plasticity and the non-synaptic trunk plasticity enables the model to successfully accommodate memory-dependent processing capabilities in a number of tasks, ranging from simple memory tests to question answering. The model can also explain contextual fear conditioning experiments, where freezing responses could be recovered by optogenetic reactivation of memory engrams under amnesia. Author summaryHow memory is organized in the brain in order to enable cognitive processing is a central open question in systems neuroscience. Traditionally, synaptic plasticity is considered the key mechanism for the establishment of memory in the brain. Recently however, this view has been questioned, and it was proposed that non-synaptic plasticity mechanisms play a more prominent role as previously considered. In this article, we propose that both, synaptic and non-synaptic plasticity are central components for the formation and utilization of memory in biological neuronal networks. Our results show that non-synaptic plasticity can act on a fast time-scale to store important information, while synaptic plasticity can adapt network function on a slow time scale in order to facilitate memory-dependent cognitive processing.

neuroscience↗

bioRxiv2018

Modulation of ACD6 dependent hyperimmunity by natural alleles of an Arabidopsis thaliana NLR resistance gene

Plants defend themselves against pathogens by activating an array of immune responses. Unfortunately, immunity programs may also cause unintended collateral damage to the plant itself. The quantitative disease resistance gene ACCELERATED CELL DEATH 6 (ACD6) serves as a nexus for the trade-off between growth and pathogen resistance in wild populations of Arabidopsis thaliana. An autoimmune allele, ACD6-Est, first identified in the natural accession Est-1, is found in over 10% of wild strains, even though it causes a clear fitness penalty under optimal growth conditions. There is, however, extensive variation in the strength of the autoimmune phenotype expressed by strains with an ACD6-Est allele, indicative of genetic modifiers. Quantitative genetic analysis suggests that the population genetic basis of ACD6 modulation is complex, with different strains often carrying different large-effect modifiers. One modifier is SUPPRESSOR OF NPR1-1, CONSTITUTIVE 1 (SNC1), located in a highly polymorphic cluster of nucleotide-binding domain and leucine-rich repeat (NLR) immune receptor genes, which are prototypes for qualitative disease resistance genes. Allelic variation at SNC1 correlates with ACD6-Est activity in multiple accessions, and a common structural variant affecting the NL linker sequence can explain differences in SNC1 activity. Taken together, we find that an NLR gene can mask the activity of an ACD6 autoimmune allele in natural A. thaliana populations, thereby linking different arms of the plant immune system.\n\nAuthor summaryPlants defend themselves against pathogens by activating immune responses. Unfortunately, these can cause unintended collateral damage to the plant itself. Nevertheless, some wild plants have genetic variants that confer a low threshold for the activation of immunity. While these enable a plant to respond particularly quickly to pathogen attack, such variants might be potentially dangerous. We are investigating one such variant of the immune gene ACCELERATED CELL DEATH 6 (ACD6) in the plant Arabidopsis thaliana. We discovered that there are variants at other genetic loci that can mask the effects of an overly active ACD6 gene. One of these genes, SUPPRESSOR OF NPR1-1, CONSTITUTIVE 1 (SNC1), codes for a known immune receptor. The SNC1 variant that attenuates ACD6 activity is rather common in A. thaliana populations, suggesting that new combinations of the hyperactive ACD6 variant and this antagonistic SNC1 variant will often arise by natural crosses. Similarly, because the two genes are unlinked, outcrossing will often lead to the hyperactive ACD6 variants being unmasked again. We propose that allelic diversity at SNC1 contributes to the maintenance of the hyperactive ACD6 variant in natural A. thaliana populations.

plant biology↗