ACS Synth Biol. 2025 Jun 6. doi: 10.1021/acssynbio.5c00036. Online ahead of print.

ABSTRACT

Engineering synthetic consortia to perform distributed functions requires robust quorum sensing (QS) systems to facilitate communication between cells. However, the current QS toolbox lacks standardized implementations, which are particularly valuable for use in bacteria beyond the model species Escherichia coli. We developed a set of three QS systems encompassing both sender and receiver modules, constructed using backbones from the SEVA (Standard European Vector Architecture) plasmid collection. This increases versatility, allowing plasmid features like the origin of replication or antibiotic marker to be easily swapped. The systems were characterized using the synthetic biology chassis Pseudomonas putida. We first tested individual modules, then combined sender and receiver modules in the same host, and finally assessed the performance across separate cells to evaluate consortia dynamics. Alongside the QS set, we provide mathematical models and rate parameters to support the design efforts. Together, these tools advance the engineering of robust and predictable multicellular functions.

PMID:40476774 | DOI:10.1021/acssynbio.5c00036

Mol Biol Evol. 2025 Jun 6:msaf145. doi: 10.1093/molbev/msaf145. Online ahead of print.

ABSTRACT

Geodia hentscheli, a species forming sponge grounds in the North Atlantic and Arctic Oceans, is a common deep-sea organism, playing a fundamental role forming biogenic habitats. However, there is little information about gene flow and adaptation patterns of this species, which is crucial to develop effective management/conservation plans under current global change scenarios. Here, we generated ddRADseq data from 110 specimens of G. hentscheli, together with microbial profiling, transcriptomics and metatranscriptomics for a selection of specimens to investigate their genetic diversity, molecular connectivity and local adaptations. Sampling covered the species' entire distribution within a wide bathymetric range. We obtained 1,115 neutral SNPs and identified long distance genetic connectivity among regions separated 1,000s of km, but strong genetic structure segregating populations by depth at ca. 1,300 m, in line with our microbial analyses. Coalescent analyses inferred the split of these depth-related genetic entities ∼10 KYA, coincident with the last post-glacial maximum. Analyses of SNPs under selection, combined with transcriptomic and metatranscriptomic data highlight the presence of several sponge genes and microbial metabolic pathways involved in adaptation to depth, including heat shock proteins and fatty acids, amongst others. The physiological plasticity of the sponge and its microbiome as a function of depth suggest the existence of a host-microbiome metabolic compensation for G. hentscheli. This study provides a multiscale paradigmatic example of the Depth Differentiation Hypothesis, a phenomenon mainly caused by changes in environmental conditions at different depths, mainly related to the presence of water masses with different characteristics, that drive local adaptations.

PMID:40476758 | DOI:10.1093/molbev/msaf145

Front Genet. 2025 May 22;16:1566675. doi: 10.3389/fgene.2025.1566675. eCollection 2025.

ABSTRACT

The growing availability of spatial transcriptomics data offers key resources for annotating query datasets using reference datasets. However, batch effects, unbalanced reference annotations, and tissue heterogeneity pose significant challenges to alignment analysis. Here, we present stGuide, an attention-based supervised graph learning model designed for cross-slice alignment and efficient label transfer from reference to query datasets. stGuide leverages supervised representations guided by reference annotations to map query slices into a shared embedding space using an attention-based mechanism. It then assigns spot-level labels by incorporating information from the nearest neighbors in the learned representation. Using human dorsolateral prefrontal cortex and breast cancer datasets, stGuide demonstrates its capabilities by (i) producing category-guided, low-dimensional features with well-mixed slices; (ii) transferring labels effectively across heterogeneous tissues; and (iii) uncovering relationships between clusters. Comparisons with state-of-the-art methods demonstrate that stGuide consistently outperforms existing approaches, positioning it as a robust and versatile tool for spatial transcriptomics analysis.

PMID:40476268 | PMC:PMC12137301 | DOI:10.3389/fgene.2025.1566675

Infect Dis Model. 2025 Apr 1;10(3):935-945. doi: 10.1016/j.idm.2025.03.009. eCollection 2025 Sep.

ABSTRACT

Professor Pierre Magal made important contributions to the field of mathematical biology before his death on February 20, 2024, including research in which epidemiological models were used to study the ends of infectious disease outbreaks. In related work, there has been interest in inferring (in real-time) when outbreaks have ended and control interventions can be relaxed. Here, we analyse data from the 2018 Ebola outbreak in Équateur Province, Democratic Republic of the Congo, during which an Ebola Response Team (ERT) was deployed to implement public health measures. We use a renewal equation transmission model to perform a quasi real-time investigation into when the ERT could be withdrawn safely at the tail end of the outbreak. Specifically, each week following the arrival of the ERT, we calculate the probability of future cases if the ERT is withdrawn. First, we show that similar estimates of the probability of future cases can be obtained from either daily or weekly case reports. This demonstrates that high temporal resolution case reporting may not always be necessary to determine when interventions can be relaxed. Second, we demonstrate how case under-reporting can be accounted for rigorously when estimating the probability of future cases. We find that, the lower the level of case reporting, the longer it is necessary to wait after the apparent final case before interventions can be removed safely (with only a small probability of additional cases). Finally, we show how uncertainty in the extent of case reporting can be included in estimates of the probability of future cases. Our research highlights the importance of accounting for under-reporting in deciding when to remove interventions at the tail ends of infectious disease outbreaks.

PMID:40475698 | PMC:PMC12138552 | DOI:10.1016/j.idm.2025.03.009

Viral Immunol. 2025 Jun 6. doi: 10.1089/vim.2025.0029. Online ahead of print.

ABSTRACT

Following reports of highly pathogenic avian influenza H5N1 infections of dairy cattle in the United States in March 2024, we established a Pan-Canadian Milk network to monitor retail milk in Canada. Milk samples from across Canada that had previously tested negative for influenza A virus (IAV) RNA were tested for the presence of anti-IAV nucleoprotein (NP) antibodies as an indicator of past infection of dairy cattle. None of the 109 milk samples tested had evidence of anti-IAV NP antibodies. This is consistent with previous findings from our academic group as well as others including federal testing initiatives that have not found any IAV RNA in milk. Although not surprising given that no cases of H5N1 in cattle have been reported in Canada to date, this work further supports that the extensive outbreak in dairy cattle in the United States has not extended northward into Canada, and the integrity of the Canadian milk supply remains intact.

PMID:40474813 | DOI:10.1089/vim.2025.0029

Int J Cancer. 2025 Aug 1;157(3):590-591. doi: 10.1002/ijc.35434. Epub 2025 Apr 18.

NO ABSTRACT

PMID:40474572 | DOI:10.1002/ijc.35434

Nat Cardiovasc Res. 2025 Jun 5. doi: 10.1038/s44161-025-00656-8. Online ahead of print.

ABSTRACT

Although genetic variant effects often interact nonadditively, strategies to uncover epistasis remain in their infancy. Here we develop low-signal signed iterative random forests to elucidate the complex genetic architecture of cardiac hypertrophy, using deep learning-derived left ventricular mass estimates from 29,661 UK Biobank cardiac magnetic resonance images. We report epistatic variants near CCDC141, IGF1R, TTN and TNKS, identifying loci deemed insignificant in genome-wide association studies. Functional genomic and integrative enrichment analyses reveal that genes mapped from these loci share biological process gene ontologies and myogenic regulatory factors. Transcriptomic network analyses using 313 human hearts demonstrate strong co-expression correlations among these genes in healthy hearts, with significantly reduced connectivity in failing hearts. To assess causality, RNA silencing in human induced pluripotent stem cell-derived cardiomyocytes, combined with novel microfluidic single-cell morphology analysis, confirms that cardiomyocyte hypertrophy is nonadditively modifiable by interactions between CCDC141, TTN and IGF1R. Our results expand the scope of cardiac genetic regulation to epistasis.

PMID:40473955 | DOI:10.1038/s44161-025-00656-8

Mol Syst Biol. 2025 Jun 5. doi: 10.1038/s44320-025-00124-2. Online ahead of print.

ABSTRACT

In response to infection or vaccination, lymph nodes must select antigen-reactive B-cells while eliminating auto-reactive B-cells. B-cells are instructed via B-cell receptor (BCR), which binds antigen, and CD40 receptor by antigen-recognizing T-cells. How BCR and CD40 signaling are integrated quantitatively to jointly determine B-cell fate decisions remains unclear. Here, we developed a differential-equations-based model of BCR and CD40 signaling networks activating NFκB. The model recapitulates NFκB dynamics upon BCR and CD40 stimulation, and when linked to established cell decision models of cell cycle and survival control, the resulting cell population dynamics. However, upon costimulation, NFκB dynamics were correctly predicted but the predicted potentiated population expansion was not observed experimentally. We found that this discrepancy was due to BCR-induced caspase activity that may trigger apoptosis in founder cells, unless timely NFκB-induced survival gene expression protects them. Iterative model predictions and sequential co-stimulation experiments revealed how complex non-monotonic integration of BCR and CD40 signals controls positive and negative selection of B-cells. Our work suggests a temporal proof-reading mechanism for regulating the stringency of B-cell selection during antibody responses.

PMID:40473841 | DOI:10.1038/s44320-025-00124-2

NPJ Sci Food. 2025 Jun 5;9(1):95. doi: 10.1038/s41538-025-00462-3.

ABSTRACT

Determining the geographic origin of palm oil in West Africa is vital for economic, environmental, and health reasons. It enhances traceability, protects local farmers, supports conservation by monitoring deforestation, and reduces food fraud, ensuring quality and regulatory compliance. Portable Raman spectroscopy offers a rapid method to identify the origin of palm oils from West Africa. Using principal component analysis (PCA), distinct clusters in scores plots were observed which reflected the geographic origin of the palm oils, with loadings from the first principal component (PC-1) highlighting β-carotene as a major source of variation among the samples. To quantify β-carotene content, a partial least squares regression (PLS-R) model was developed in coconut oil as the base oil as it is known to be β-carotene free. Once calibrated, PLS-R was used to rank the palm oil from West Africa based on their β-carotene levels. The resulting models in coconut oil demonstrated strong linearity and predictive performance, with R² and Q² values of 0.9848 and 0.9552, respectively, alongside low root mean square errors of cross-validation (0.1282 mM) and prediction (0.0747 mM); moreover, this model allows the palm oils to be ranked based on β-carotene content which was entirely reflective of the oils position in PC-1 from PCA. These findings underscore the potential of Raman spectroscopy as an effective tool for authenticating the geographic origin of palm oil from West Africa.

PMID:40473674 | DOI:10.1038/s41538-025-00462-3

Nat Commun. 2025 Jun 5;16(1):5248. doi: 10.1038/s41467-025-60535-5.

ABSTRACT

SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes displace nucleosomes to promote the access of transcription factors to enhancers and promoters. Despite the critical roles of SWI/SNF in animal development and tumorigenesis, how signaling pathways recruit SWI/SNF complexes to their target genes is unclear. Here, we demonstrate that target gene activation mediated by β-catenin, the essential transcriptional coactivator in the Wnt signal transduction pathway, requires ubiquitylation of the SWI/SNF component Brahma-related gene-1 (BRG1) by the E3 ubiquitin ligase Thyroid Hormone Receptor Interactor 12 (TRIP12). TRIP12 depletion in Drosophila, zebrafish, mouse organoids, and human cells attenuates Wnt signaling. Genetic epistasis experiments place TRIP12 activity downstream of the β-catenin destruction complex. TRIP12 interacts with and ubiquitylates BRG1, and BRG1 depletion blocks TRIP12-mediated Wnt pathway activation. TRIP12 promotes BRG1 binding to β-catenin in the presence of Wnt. Our findings support a model in which TRIP12 ubiquitylates BRG1 in the presence of Wnt and promotes its interaction with β-catenin in the nucleus, in order to recruit SWI/SNF to Wnt target genes. Our studies suggest a general mechanism by which cell signaling induces the interaction between BRG1 and pathway-specific transcription factors to recruit SWI/SNF complexes to their appropriate target genes.

PMID:40473626 | DOI:10.1038/s41467-025-60535-5

Eur Respir J. 2025 Jun 5:2401667. doi: 10.1183/13993003.01667-2024. Online ahead of print.

ABSTRACT

The formation of myofibroblast foci constitutes a hallmark pathological feature of idiopathic pulmonary fibrosis (IPF), yet the mechanism remains elusive. RNA binding motif single-stranded interacting protein 1 (RBMS1), is known to be essential for proliferation and cell cycle progression; however, its role in pulmonary fibrosis remains to be clarified.This study aimed to systematically elucidate the role and underlying mechanism of RBMS1 in pulmonary fibrosis utilising mouse primary lung fibroblasts (mPLFs), fibroblast-specific Rbms1 deletion and overexpression mice models, and lung samples from IPF patients.RBMS1 was highly expressed in both IPF patient lungs and murine bleomycin (BLM)-induced fibrotic lesions. Notably, elevated RBMS1 expression was observed in the cytoplasm of mPLFs following TGF-β1 stimulation. Rbms1 promoted lung fibroblast activation, while knockdown of Rbms1 mitigated TGF-β1-induced fibrogenesis. In vivo, overexpression impaired lung function and exacerbated pulmonary fibrosis, whereas fibroblast-specific Rbms1 deletion exhibited a significant reduction in fibrosis post-BLM treatment. Mechanistically, Rbms1 binds to Sumo2 3'UTR, enhancing the mRNA stability. Furthermore, Rbms1 induced the SUMOylation of Smad4, with lysine 158 identified as a critical SUMOylation site. Meanwhile, Sumo2 knockdown alleviated the Rbms1-driven exacerbation of pulmonary fibrosis. Importantly, the nortriptyline pharmacologically inhibited RBMS1 to ameliorate pulmonary fibrosis in mice.Collectively, our study sheds light on the regulatory role of RBMS1 in pulmonary fibrosis, highlighting its therapeutic potential for targeted antifibrotic strategies.

PMID:40473311 | DOI:10.1183/13993003.01667-2024

Plant Physiol. 2025 Jun 6:kiaf232. doi: 10.1093/plphys/kiaf232. Online ahead of print.

NO ABSTRACT

PMID:40473241 | DOI:10.1093/plphys/kiaf232

Protein Expr Purif. 2025 Jun 3:106752. doi: 10.1016/j.pep.2025.106752. Online ahead of print.

ABSTRACT

The yeast cadmium factor 1 protein (Ycf1p) is an ATP-binding cassette (ABC) transporter located in the vacuolar membrane and is responsible for transporting glutathione-conjugated metals from the cytoplasm into the vacuole. Ycf1p contains the ABC core structure of two transmembrane domains (TMD1, TMD2) and two nucleotide-binding domains (NBD1, NBD2). As a member of the C-subfamily of ABC proteins (ABCC), Ycf1p also contains an N-terminal extension comprised of an additional TMD (TMD0) and L0 linker. Although high-resolution structures of many ABC transporters have been determined, the NBDs can be at low resolution in cryo-EM maps and thus, studies of the isolated cytosolic NBDs are crucial for obtaining molecular-level details of the dynamics of these catalytic entities, for example. In this study, we present a scheme for obtaining samples of NBD2 from the yeast cadmium factor protein 1 (Ycf1p) in a soluble, monomeric, and functional form. While production of NBD1 from Ycf1p and other ABC proteins has been accomplished, generating samples of NBD2 from different ABC proteins has been elusive for the most part, particularly for ABCC proteins. We show that NBD2 preparation necessitates minimizing dimerization and aggregation of the protein at multiple steps during the purification, which is accomplished by employing a solubility tag, eliminating nucleotides from the buffers, and limiting the duration of spin concentrating steps. This work lays the foundation for detailed studies of Ycf1p NBD2 and provides an outline for optimizing the generation of NBD2 from other ABC proteins.

PMID:40473008 | DOI:10.1016/j.pep.2025.106752

Bioorg Med Chem Lett. 2025 Jun 3:130293. doi: 10.1016/j.bmcl.2025.130293. Online ahead of print.

ABSTRACT

The papain-like protease (PLpro) of SARS-CoV-2 has been identified as a pivotal enzyme in viral replication, indicating it a promising target for drug discovery. Utilizing a virtual screening strategy, compound 1 with the N-(3-(5-amino-1H-pyrazol-3-yl)phenyl) benzenesulfonamide scaffold was discovered as a hit targeting PLpro. Structural modification from virtually screened hit 1 led to the development of a series of substituted 3-phenyl-1H-5-pyrazolylamide derivatives. Notably, compounds 14 h and 14e exhibited improved PLpro inhibitory activity (IC50 = 14.2 μM and 12.0 μM, respectively) and low cytotoxicity. Further biological evaluation revealed that compound 14e with a thiophene aldehyde group displayed potent binding activity (KD = 1.86 μM). This 3-phenyl-1H-5-pyrazolylamide scaffold offers significant potential for further development as a novel class of PLpro inhibitors.

PMID:40473007 | DOI:10.1016/j.bmcl.2025.130293

Cell Syst. 2025 Jun 2:101300. doi: 10.1016/j.cels.2025.101300. Online ahead of print.

ABSTRACT

Systems biology offers a view of the cell as an input-output device: a biochemical network (or cellular "processor") that interprets cues from the microenvironment to drive cell fate. Advancements in single-cell technologies are unlocking the cellular black box, revealing heterogeneity in seemingly homogeneous cell populations. But are these differences technical variability or biology? In this review, we explore this question through a systems biology lens, offering a framework for conceptualizing heterogeneity from the cell's perspective and summarizing systems and synthetic biology tools for capturing heterogeneity. While cellular inputs shape the probability of attaining particular fates, each cell spins a stochastic "wheel of fate." Applying this framework, we explore heterogeneity in two case studies: human pluripotent stem cell (hPSC) culture and beta cell differentiation. Looking forward, we discuss how a systems approach to heterogeneity may enable more predictable outcomes in stem cell research, with broad implications for developmental biology and regenerative medicine.

PMID:40472847 | DOI:10.1016/j.cels.2025.101300

IET Syst Biol. 2025 Jan-Dec;19(1):e70015. doi: 10.1049/syb2.70015.

ABSTRACT

ADAMTS5, a member of the ADAMTS family, exhibits crucial biological roles, including protein shedding, proteolysis, and cell migration. Its relevance in breast cancer (BC) was explored through an integrative approach combining high-throughput analyses, database validations, and experimental confirmation. ADAMTS5 expression was significantly reduced in BC samples, as verified by microarray analysis, qRT-PCR, and public database resources. A protein-protein interaction network revealed five proteins-COL10A1, COL11A1, COMP, MMP1 and SDC1-that interact with ADAMTS5 and are primarily associated with the ECM-receptor interaction pathway. These proteins also engage in cell cycle checkpoint signalling, emphasising their potential role in tumour progression. Survival analysis of BC samples identified a novel prognostic signature based on ADAMTS5-related proteins. The study extended to coding and noncoding RNA interactions, identifying lncRNAs as key regulators. CRNDE acts as a ceRNA for ADAMTS5, modulating its expression via hsa-miR-135b-3p. Meanwhile, BAIAP2-AS1 interacts directly with ADAMTS5, offering another layer of regulatory control and prognostic value. These findings position ADAMTS5 as a vital player in BC biology, with its low expression linked to critical pathways and survival outcomes. The identified lncRNA-mediated regulatory mechanisms add depth to understanding ADAMTS5's role and suggest potential targets for therapeutic development. This study underscores ADAMTS5's potential as a biomarker and its broader implications in unravelling BC molecular mechanisms.

PMID:40472834 | DOI:10.1049/syb2.70015

J Environ Manage. 2025 Jun 4;389:126075. doi: 10.1016/j.jenvman.2025.126075. Online ahead of print.

ABSTRACT

The spread of aquatic invasive species (AIS) presents a pressing challenge for global biodiversity, with freshwater ecosystems being particularly affected. The connection of watersheds throughout Europe by the construction of artificial shipping canals has created novel invasion pathways, but may also provide critical infrastructure to counter range expansion by implementation of different barrier solutions. Here, we critically review the efficacy, applicability and limitations of dispersal barriers against AIS in shipping canals considering fishes, invertebrates, algae, bacteria and fungi. Despite the wide spread of AIS and their known detrimental effects on aquatic ecosystems, research focusing on barriers for AIS in shipping canals is rather limited and predominantly concentrated on a few species of fish. Out of 180 screened studies, only 32 examined the efficacy of technologies such as electric fields, acoustic signals, strobe light, air-bubble curtains, CO2 and pheromones as non-physical barriers. Efficacy and applicability was mostly tested in laboratory setups and strongly species-dependent, requiring a site-specific identification of the most useful barrier technology. Major limitations to barrier implementation include undesired and unknown side effects on non-target species, humans and the environment. To preserve the ecological integrity of freshwater ecosystems across transboundary and inland watersheds, future research should tackle these challenges by increasing the number of studies under realistic field conditions to allow evidence-based decision making on the management of AIS.

PMID:40472533 | DOI:10.1016/j.jenvman.2025.126075

Comput Biol Med. 2025 Jun 3;194:110456. doi: 10.1016/j.compbiomed.2025.110456. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Coronary heart disease (CHD) is a leading cause of morbidity and mortality globally, frequently accompanied by major depressive disorder (MDD), which exacerbates clinical outcomes. While Guanxinning (GXN) has demonstrated efficacy in improving cardiac function and reducing angina symptoms in CHD patients, its potential role in alleviating MDD symptoms has not been extensively studied. This study aims to explore the potential therapeutic effects of GXN on CHD and MDD through the regulation of S1PR3.

METHODS: We utilized bioinformatics, network pharmacology, and Mendelian randomization to identify S1PR3 as a key therapeutic target for CHD and MDD. Molecular docking simulations were conducted to validate the binding affinity between GXN components and S1PR3.

RESULTS: Our findings indicate that CHD is a risk factor for MDD, and the downregulation of S1PR3 expression in CHD patients is associated with the onset of MDD. Molecular docking analysis demonstrated that GXN can effectively bind to S1PR3, suggesting that GXN may modulate S1PR3 expression levels to prevent MDD in CHD patients.

CONCLUSION: This study identifies S1PR3 as a critical therapeutic target for the comorbidity of CHD and MDD. GXN has the potential to treat CHD and MDD by regulating S1PR3 expression levels. Although further validation through animal and cell-based experiments is needed, our findings provide a foundational understanding of the molecular mechanisms and highlight the therapeutic potential of GXN in dual heart therapy.

PMID:40472508 | DOI:10.1016/j.compbiomed.2025.110456

Blood Adv. 2025 Jun 5:bloodadvances.2025016209. doi: 10.1182/bloodadvances.2025016209. Online ahead of print.

ABSTRACT

Platelets fulfill their essential physiological roles sensing the extracellular environment through their membrane proteins. The native membrane environment provides essential regulatory cues that impact the protein structure and mechanism of action. Single-particle cryogenic electron microscopy (cryo-EM) has transformed structural biology by allowing high-resolution structures of membrane proteins to be solved from homogeneous samples. Our recent breakthroughs in data processing now make it feasible to obtain atomic-level-resolution protein structures from crude preparations in their native environments by integrating cryo-EM with the "Build-and-Retrieve" (BaR) data processing methodology. We applied this iterative bottom-up methodology on resting human platelet membranes for an in-depth systems biology approach to uncover how lipids, metal binding, post-translational modifications, and co-factor associations in the native environment regulate platelet function at the molecular level. Here, we report using cryo-EM followed by the BaR method to solve the unmodified integrin αIIbβ3 structure directly from resting human platelet membranes in its inactivated and intermediate states at 2.75Å and 2.67Å, respectively. Further, we also solved a novel dimer conformation of αIIbβ3 at 2.85Å formed by two intermediate-states of αIIbβ3. This may indicate a previously unknown self-regulatory mechanism of αIIbβ3 in its native environment. In conclusion, our data show the power of using cryo-EM with the BaR method to determine three distinct structures including a novel dimer directly from natural sources. This approach allows us to identify unrecognized regulation mechanisms for proteins without artifacts due to purification processes. These data have the potential to enrich our understanding of platelet signaling circuitry.

PMID:40472320 | DOI:10.1182/bloodadvances.2025016209

Elife. 2025 Jun 5;13:RP94586. doi: 10.7554/eLife.94586.

ABSTRACT

A classic problem in metabolism is that fast-proliferating cells use seemingly wasteful fermentation for energy biogenesis in the presence of sufficient oxygen. This counterintuitive phenomenon, known as overflow metabolism or the Warburg effect, is universal across various organisms. Despite extensive research, its origin and function remain unclear. Here, we show that overflow metabolism can be understood through growth optimization combined with cell heterogeneity. A model of optimal protein allocation, coupled with heterogeneity in enzyme catalytic rates among cells, quantitatively explains why and how cells choose between respiration and fermentation under different nutrient conditions. Our model quantitatively illustrates the growth rate dependence of fermentation flux and enzyme allocation under various perturbations and is fully validated by experimental results in Escherichia coli. Our work provides a quantitative explanation for the Crabtree effect in yeast and the Warburg effect in cancer cells and can be broadly used to address heterogeneity-related challenges in metabolism.

PMID:40472190 | DOI:10.7554/eLife.94586