Biology subjects

Hesselberg-Thomsen, V.

Publications and source records attributed to Hesselberg-Thomsen, V..

4 recordsLinked to original sources

bioRxiv2026

Metabolic exchange and siderophore sharing underlie emergent biofilm synergism

Biofilm communities exhibit emergent properties that exceed the sum of contributions from individual members of the community. Here, we describe a multilayered metabolic interaction that drives enhanced biofilm formation among three bacterial species from the plant rhizosphere. Comparative metatranscriptomic and metabolomic analyses reveal that Bacillus velezensis-secreted 5-aminovaleric acid promotes the growth of the other community members, Burkholderia contaminans and Acinetobacter baumannii. In return, B. contaminans supplies branched-chain amino acids for B. velezensis. Branched-chain amino acids and cell-cell signaling acyl-homoserine lactones from B. contaminans induce biosynthesis of the siderophore bacillibactin in B. velezensis, that is further enhanced by A. baumannii. In exchange, the B. velezensis-secreted siderophore promotes the growth of B. contaminans in iron-limited conditions, which benefits the multispecies biofilm community in vitro and promotes plant growth performance in iron-depleted soil. Our study reveals the molecular mechanisms underlying an emergent rhizosphere biofilm community function and demonstrates its importance in plant-microbe interactions.

microbiology↗

bioRxiv2024

Kinetic-model-guided engineering of multiple S. cerevisiae strains improves p-coumaric acid production

The use of kinetic models of metabolism in design-build-learn-test cycles is limited despite their potential to guide and accelerate the optimization of cell factories. This is primarily due to difficulties in constructing kinetic models capable of capturing the complexities of the fermentation conditions. Building on recent advances in kinetic-model-based strain design, we present the rational metabolic engineering of an S. cerevisiae strain designed to overproduce p-coumaric acid (p-CA), an aromatic amino acid with valuable nutritional and therapeutic applications. To this end, we built nine kinetic models of an already engineered p-CA-producing strain by integrating different types of omics data and imposing physiological constraints pertinent to the strain. These nine models contained 268 mass balances involved in 303 reactions across four compartments and could reproduce the dynamic characteristics of the strain in batch fermentation simulations. We used constraint-based metabolic control analysis to generate combinatorial designs of 3 enzyme manipulations that could increase p-CA yield on glucose while ensuring that the resulting engineering strains did not deviate far from the reference phenotype. Among 39 unique designs, 10 proved robust across the phenotypic uncertainty of the models and could reliably increase p-CA yield in nonlinear simulations. We implemented these top 10 designs in a batch fermentation setting using a promoter-swapping strategy for down-regulations and plasmids for up-regulations. Eight out of the ten designs produced higher p-CA titers than the reference strain, with 19 - 32% increases at the end of fermentation. All eight designs also maintained at least 90% of the reference strains growth rate, indicating the critical role of the phenotypic constraint. The high experimental success of our in-silico predictions lays the foundation for accelerated design-build-test-learn cycles enabled by large-scale kinetic modeling.

systems biology↗

bioRxiv2024

Surfactin facilitates the establishment of Bacillus subtilis in synthetic communities

Soil bacteria are prolific producers of a myriad of biologically active secondary metabolites. These natural products play key roles in modern society, finding use as anti-cancer agents, as food additives, and as alternatives to chemical pesticides. As for their original role in interbacterial communication, secondary metabolites have been extensively studied under in vitro conditions, revealing a multitude of roles including antagonism, effects on motility, niche colonization, signaling, and cellular differentiation. Despite the growing body of knowledge on their mode of action, biosynthesis, and regulation, we still do not fully understand the role of secondary metabolites on the ecology of the producers and resident communities in situ. Here, we specifically examine the influence of Bacillus subtilis-produced cyclic lipopeptides (LPs) during the assembly of a bacterial synthetic community (SynCom), and simultaneously, explore the impact of LPs on B. subtilis establishment success in a SynCom propagated in an artificial soil microcosm. We found that surfactin production facilitates B. subtilis establishment success within multiple SynComs. Surprisingly, while neither a wild type nor a LP non-producer mutant had major impact on the SynCom composition over time, the B. subtilis and the SynCom metabolomes are both altered during co-cultivation. Overall, our work demonstrates the importance of surfactin production in microbial communities, suggesting a broad spectrum of action of this natural product.

microbiology↗

bioRxiv2024

Pseudo batch transformation: A novel method to correct for mass removal through sample withdrawal of fed-batch fermentations

SummaryWe present a novel "pseudo batch" transformation algorithm that maps analytical data obtained for fed-batch bioreactor cultivations onto a constant volume batch process, significantly decreasing the complexity of characterizing the fed-batch process. Availability and implementationOur method is implemented in both Excel and Python and is available with tutorials and example data from https://github.com/biosustain/pseudobatch. The Python package is also available on PYPI under the name "pseudobatch". ContactLars Keld Nielsen, e-mail: lars.nielsen@uq.edu.au Supplementary informationA comprehensive explanation of the simulated fed-batch, parameter estimation procedures, and the Bayesian model can be found in supplementary information (S1-S5).

bioinformatics↗