Biology subjects

Priem, B.

Publications and source records attributed to Priem, B..

3 recordsLinked to original sources

bioRxiv2026

Drug-tolerant persister cells reallocate carbon sources to fuel antioxidant metabolism for survival

Therapy resistance is the leading cause of cancer-related deaths. Drug-tolerant persister cells (DTPs) represent a major barrier to cancer cure, mediating resistance through adaptive cell state transitions and driving tumor progression. Here, we investigate metabolic differences between DTPs and drug-sensitive cancer cells using integrated fluxomics. Proteomic profiling and extracellular flux analyses revealed that DTPs upregulate glycolysis and gluconeogenesis while reducing oxidative phosphorylation, indicating a shift in central carbon metabolism. Isotope tracing and metabolic modeling demonstrate that DTPs utilize glucose to fuel the pentose phosphate pathway (PPP) to generate NADPH and metabolize glutamine to provide carbons for the PPP via gluconeogenesis. Integrating our multi-omic datasets into a genome-scale model identified that DTPs sustain antioxidant metabolism by decreasing fluxes of other NADPH-consuming reactions upon in silico PPP knockout. These findings reveal a systems-level shift in DTP metabolism that maintains antioxidant activity for cell survival, highlighting potential new targets and treatment paradigms to overcome therapy resistance.

cancer biology↗

bioRxiv2025

A community-consensus reconstruction of Chinese Hamster metabolism enables structural systems biology analyses to decipher metabolic rewiring in lactate-free CHO cells

Genome-scale metabolic models (GEMs) are indispensable for studying and engineering cellular metabolism. Here, we present iCHO3K, a community-consensus, manually-curated reconstruction of the Chinese Hamster metabolic network. In addition to accounting for 11004 reactions associated with 3597 genes, iCHO3K includes 3489 protein structures and structural descriptors for >70% of its 7377 metabolites, enabling deeper exploration of the link between molecular structure and cellular metabolism. We used iCHO3K to contextualize transcriptomics and metabolomics data from a CHO cell line in which lactate secretion is abolished. We found the reduced glycolytic flux and enhanced TCA cycle flux were accompanied by an elevated NADH and PEP levels in these cells, consistent with experimental measurements. Leveraging iCHO3Ks structural annotations, we identified candidate binding interactions of NADH and PEP with glycolytic enzymes showing model-predicted differential flux, suggesting novel allosteric regulation associated with the observed decrease in glucose uptake and glycolysis. Overall, iCHO3K offers a valuable framework for systematic integration of omics data, improved flux predictions, and structure-guided insights, thus advancing CHO cell engineering and enhancing biomanufacturing efficiency.

systems biology↗

bioRxiv2021

Low cost and sustainable hyaluronic acid production in a manufacturing platform based on Bacillus subtilis 3NA strain

Hyaluronic acid (HA) is a high value glycosaminoglycan mostly used in health and cosmetic applications. Commercial HA is produced from animal tissues or in toxigenic bacteria of the genus Streptococcus grown in complex media, which are expensive and raise environmental concerns due to the disposal of large amounts of broth with high organic loads. Other microorganisms were proposed as hosts for the heterologous production of HA, but the methods are still costly. The extraordinary capacity of this biopolymer to bind and retain water attracts interest for large scale applications where biodegradable materials are needed, but its high cost and safety concerns are barriers for its adoption. Bacillus subtilis 3NA strain is prototrophic, amenable for genetic manipulation, GRAS, and can rapidly reach high cell densities in salt-based media. These phenotypic traits were exploited to create a platform for biomolecule production using HA as a proof of concept. First, the 3NA strain was engineered to produce HA; second, a chemically defined medium was formulated using commodity-priced inorganic salts combined at the stoichiometric ratios needed to build the necessary quantities of biomass and HA; and third, a scalable fermentation process, where HA can be produced at the maximum volumetric productivity (VP), was designed. A comparative economic analysis against other methods indicates that the new process may increase the operating profit of a manufacturing plant by more than 100 %. The host, the culture medium, and the rationale employed to develop the fermentation process described here, introduce an IP free platform that could be adaptable for production of other biomolecules. Key PointsO_LIA platform for the production of biomolecules was designed based on B. subtilis 3NA, a chemically defined medium and a fermentation process. C_LIO_LIAs proof of concept, high quality hyaluronic acid was produced with an environmentally friendly process. C_LIO_LIA techno-economic analysis indicates that the process is more that 100% profitable than current methods. C_LI

bioengineering↗