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Potential of indigenous crop microbiomes for sustainable agriculture NFD

Potential of indigenous crop microbiomes for sustainable agriculture NFD | RMH | Scoop.it
The intimate interactions of indigenous crops with their associated microbiomes during long-term co-evolution strengthen the capacity and flexibility of crops to cope with biotic and abiotic stresses. This represents a promising untapped field for searching novel tools to sustainably increase crop productivity. However, the current capability of harnessing the power of indigenous crop microbiomes for sustainable crop production is limited due to low efficiency of separating the targeted functional microbes. Here, we highlight the potential benefits and existing challenges of utilizing indigenous crop microbiomes to reduce agrochemical inputs and increase crop resistance to biotic and abiotic stresses. We propose a framework using Raman-spectroscopy-based single-cell-sorting technology combined with a synthetic community approach to design and optimize a functionally reliable ‘beneficial biome’ under controlled conditions. This framework will offer opportunities for sustainable agriculture and provide a new direction for future studies. Crop microbiomes provide plants with beneficial functions including increased nutrient acquisition and stress tolerance, but the current capability of utilizing indigenous crop microbiomes is limited due to low efficiency of separating the targeted functional microbes. A newly proposed framework using single-cell-sorting Raman spectroscopy combined with a synthetic community approach has the potential to design and optimize a ‘beneficial biome’.
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Biomolecular condensation using de novo designed globular proteins | brvsb

Biomolecular condensation using de novo designed globular proteins | brvsb | RMH | Scoop.it

De novo protein design is advancing rapidly, but many targets remain inaccessible to current AI-based tools. Here we describe de novo designed globular domains that drive biomolecular condensation. Starting from a water-soluble, monomeric protein, we make variants with the same amino-acid composition but different surface-charge distributions: one with large patches of surface charge, and another with a more-homogeneous charge distribution. The individual domains form stable and discrete structures in solution, with the large-patch variant exhibiting more-attractive interprotein interactions. Next, two copies of each variant are joined with disordered linkers to generate dumbbell-like proteins. When expressed in eukaryotic cells, the large-patch variant forms intracellular puncta, whereas that with small patches does not. The assemblies are dynamic, liquid condensates in vitro and in cells. The structured domains facilitate functionalisation: we introduce fluorophore-binding sites to visualize fluorescent condensates directly in cells without a GFP reporter; and we manipulate the condensates using motor proteins.

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llps

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Evolutionary Decoding of the Bacillus subtilis Secretome: Insights from Pan-Genomics and Deep Learning | brvsys

Evolutionary Decoding of the Bacillus subtilis Secretome: Insights from Pan-Genomics and Deep Learning | brvsys | RMH | Scoop.it

Bacillus subtilis serves as a crucial host for industrial protein production, where the efficiency and regulation of its secretion system represent a central focus of applied research. Despite substantial genomic diversity among strains, current understanding of signal peptides, which are key elements in the secretion process, remains largely based on single model strains, lacking systematic investigation from a pan-genomic perspective. This study integrates pan-genomics and deep learning to construct a pan-secretome profile of 287 B. subtilis strains. Our analysis reveals an open repertoire of signal peptides in B. subtilis. Our results reveal an open pan-signal peptidome in B. subtilis. Core signal peptides exhibit high sequence conservation and primarily direct the localization of housekeeping proteins, whereas accessory signal peptides govern the extracellular secretion of environment-responsive proteins, forming a functional housekeeping-adaptive dichotomy. We demonstrated at a broad scale the widespread evolutionary decoupling between signal peptides and their corresponding mature peptides, uncovering a modular evolutionary mechanism in protein evolution. While the deep learning model achieved high accuracy (88.0%) in discriminating core and accessory gene-encoded full-length proteins, its performance was considerably limited when using signal peptide sequences alone (69.7% accuracy), reflecting the information constraints inherent to short sequences. This study provides a systematic portrayal of the signal peptide evolutionary landscape in B. subtilis at the pan-genome scale, advancing our understanding of the evolutionary principles governing bacterial secretion systems and establishing a theoretical foundation for optimizing industrial protein production through rational signal peptide design.

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A balance between environmental filtering and competitive exclusion modulates the macroecology of alternative stable states in microbial communities | brveco

A balance between environmental filtering and competitive exclusion modulates the macroecology of alternative stable states in microbial communities | brveco | RMH | Scoop.it

Predicting the assembly and stability of microbial ecosystems is fundamentally challenged by the stochasticity inherent in historical contingencies. Although these dynamics often appear reproducible at coarse taxonomic or functional scales, the mechanisms governing fine-grained species-level variation and the emergence of alternative stable states remain an unresolved problem in ecology. Bridging the gap between individual species variability and the emergence of predictable community-level attractors is essential for a mechanistic understanding of ecosystem resilience. Here, by analyzing replicate microbial communities assembled in vitro, we demonstrate that community structure is built upon individual species exhibiting robustly bimodal abundance distributions. Each taxon exists in either a high- or low-abundance state. We show that the collective configuration of these binary species states - a phenomenon also observed in natural systems - drives the correlation structure between community members and defines a set of discrete, alternative community-level attractors. By examining the prevalence of species across these attractors, we uncover a striking taxonomic signal: phylogenetically close relatives are significantly more likely to display reciprocal prevalence patterns - where the dominance of one relative necessitates the suppression of the other - than expected by chance. This discovery directly rejects models based on simple functional redundancy. Instead, it proves that state-dependent competitive exclusion is a primary driver of community divergence, where the identity of the ``winner'' is contingent on the collective state of the entire community. Our work reframes microbial community structure through the lens of discrete population states, providing a predictive framework for understanding ecosystem stability and the engineering of community functions.

?'s insight:

microbial assembly rule

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Remediation and upcycling of microplastics by algae with wastewater nutrient removal and bioproduction potential | Ncm

Remediation and upcycling of microplastics by algae with wastewater nutrient removal and bioproduction potential | Ncm | RMH | Scoop.it

Microplastics have emerged as major environmental hazards that require efficient, cost-effective, and sustainable remediation technologies. This study introduces an integrative platform for the remediation and upcycling of microplastics by algae, while synergizing with plastic upcycling, wastewater treatment, and algal production. The strategy employs a mechanism that enhances hydrophobic interactions between the cell surface and microplastics, enabling rapid aggregation and removal. The platform achieves a superior microplastic removal efficiency of 91.4% within 1 hour, with a capacity of 0.1-gram microplastic per gram of biomass. Furthermore, the study demonstrates an upcycling strategy that converts microplastics-enriched cyanobacteria into plastic composites with unique performance. This work also integrates microplastic removal with cyanobacterial bioproduction and wastewater treatment, offering an approach that synergizes remediation with these value-added processes. Ultimately, this platform provides a viable and sustainable pathway to address microplastic pollution by creating value through plastic upcycling, wastewater nutrient removal, and CO2-based bioproduction. Microplastics (MPs) represent an environmental hazard which must be resolved by efficient, cheap, and sustainable remediation technology. Here the authors use an engineered algae to capture MPs and treat wastewater, the captured algae-plastic mix is upcycled into a tougher bioplastic composite.

?'s insight:

1str, bioremediation, plastic, hydrophobic cyano engineered for limonene production. the produced limonene was found to be secreted and enriched on the cell surface before volatilizing, thereby increasing cell hydrophobicity.

hydrophobic cell surface could effectively interact with the hydrophobic portion of the plastic surface, leading to cell-microplastic aggregation, co-sedimentation. 

the removed microplastics could be upcycled together with cyanobacterial biomass to make a plastic composite

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Microplastic biofilm as hotspots of antibiotic resistance genes and potential pathogens | npj

Microplastic biofilm as hotspots of antibiotic resistance genes and potential pathogens | npj | RMH | Scoop.it

Microplastic biofilms, known as the “plastisphere”, harbor diverse microbial communities and serve as reservoirs for antibiotic resistance genes (ARGs). This review discussed the mechanisms driving bacterial community alteration on microplastics and delineated the pathways through which ARGs transfer within microplastic biofilms. We expected to provide a comprehensive understanding of the ecological and human health impacts associated with microplastic biofilms and ARGs, thereby informing strategies to mitigate plastic pollution and its risks.

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December 21, 11:07 PM
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Deciphering the molecular roles of antimicrobial peptides in plant innate immunity and their potential applications in crop protection

Deciphering the molecular roles of antimicrobial peptides in plant innate immunity and their potential applications in crop protection | RMH | Scoop.it
Plants rely heavily on a complex innate immune system to repel microbial attacks, and antimicrobial peptides (AMPs) play a crucial role as central immune modulators of their immune response. These small, structurally diverse molecules exhibit broad-spectrum activities against bacteria, fungi, viruses, and nematodes through direct membrane disruption, interference with intracellular targets, and modulation of host signaling networks. Recent progress in multi-omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, combined with synthetic biology, has led to a significant increase in our understanding of classification, biosynthetic pathways, structure-function relationships, and the regulatory integration of AMPs within pattern-triggered immunity (PTI) and effector-triggered immunity (ETI). Some of these latter tools accelerate rational peptide design and enable applications in agriculture: among others, transgenic crops possessing constitutive or pathogen-inducible AMP expression, as well as peptide-based agrochemicals, represent eco-friendly alternatives to classical pesticides. Despite such breakthroughs, major challenges persist that currently limit large-scale deployment: rapid pathogen evolution of resistance, insufficient target specificity, peptide instability under field conditions, potential phytotoxicity, and complex regulatory approval pathways. Such barriers will require integrated systems-biology approaches, improved delivery platforms, for example, nanotechnology or bioencapsulation, and precise engineering of AMP-host interactions. This review consolidates current information on plant AMPs, highlighting transformative multi-omics insights and critically assessing the remaining hurdles to be overcome for the full utilization of AMPs in next-generation sustainable crop protection and global food security.
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December 21, 1:07 PM
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Engineered probiotics platform for oral delivery of antibody as a high-compliance alternative for immune-mediated inflammatory diseases

Engineered probiotics platform for oral delivery of antibody as a high-compliance alternative for immune-mediated inflammatory diseases | RMH | Scoop.it
Antibody-based therapies have transformed the management of immune-mediated inflammatory diseases (IMIDs), but the need for frequent injections often leads to inadequate patient adherence and suboptimal long-term disease control. To address this challenge, we develop AIDEN (aid for IMIDs: engineered EcN), an engineered probiotic platform that enables oral delivery of therapeutic antibodies using synthetic biology. In this study, we assess the efficacy of AIDEN-IL17, a variant designed to secrete single-chain variable fragments targeting interleukin-17A (IL-17A), in murine models of psoriasis and inflammatory bowel disease. AIDEN-IL17 exhibits stable gut colonization and sustained in situ antibody production, resulting in moderate reduction of systemic IL-17A levels and significant amelioration of disease symptoms. Notably, the AIDEN platform is modular and adaptable for delivering a broad range of antibody therapeutics, offering a promising, patient-friendly strategy for the treatment of IMIDs.
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December 21, 12:54 PM
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Exploring single-cell biosynthetic noise and dynamics for enhanced betaxanthin production in Escherichia coli | Ncm

Exploring single-cell biosynthetic noise and dynamics for enhanced betaxanthin production in Escherichia coli | Ncm | RMH | Scoop.it

Cell-to-cell variability often limits the efficiency of microbial bioproduction, yet how individual cells fluctuate over time and how these fluctuations shape population-level output remain unclear. To address this issue, we tracked a heterologous betaxanthin pathway in Escherichia coli using microfluidics-assisted time-lapse microscopy, allowing simultaneous measurement of fluctuations in betaxanthin, its biosynthetic enzyme DOD and growth across generations. Here we show that over 50% of high betaxanthin producers become medium or low producers after two divisions. Betaxanthin variation primarily originates from DOD noise, with a smaller contribution from growth rate fluctuations. We further develop a stochastic model to explore various control circuits and find that pathway enzyme or metabolite-based growth selection strategies are most effective in enhancing production. We experimentally validate the model by coupling enzyme expression to nutrient availability, which enriches high producers and boosts titer by 4.4-fold. Our results highlight key sources of metabolic heterogeneity and provide a framework for designing robust microbial processes. Cell-to-cell variability limits efficient microbial production. Here, the authors track single cells to reveal enzyme noise as the main source of bioproduction variation, and by coupling growth to pathway performance, they selectively enrich high producers and substantially boost overall titres.

?'s insight:

2st, heterogeneity, fuzhong, meng control methods,

we developed a stochastic model for single-cell protein and metabolite production based on the betaxanthin pathway. Briefly, the model includes four molecular species: DOD protein (p), the pathway precursor L-DOPA (d), the metabolite product betaxanthin (m), and a growth factor (γ) fused a mCherry to the DOD enzyme to track enzyme expression dynamics.

formamidase (FmdA) from Paenibacillus pasadenensis as the selection gene. FmdA catalyzes the hydrolysis of formamide, a nitrogen-rich compound not metabolizable by E. coli, into ammonium. Cells that stochastically express high levels of FmdA generate more ammonia and thus grow faster in selection medium where formamide is the sole nitrogen source. To couple growth to DOD expression, we cloned a codon-optimized FmdA downstream of the DOD-mCherry operon

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December 21, 11:19 AM
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Engineering and characterization of small-molecule transporters for cell factories | Tin

Engineering and characterization of small-molecule transporters for cell factories | Tin | RMH | Scoop.it
Membrane transporters play crucial roles in metabolite exchange, cellular communication, and metabolic homeostasis and are attractive targets in metabolic engineering for the development of microbial cell factories. While transporter engineering has proven effective in enhancing nutrient uptake, improving product secretion, and optimizing metabolic flux, its broader application is limited by incomplete knowledge of membrane transport systems and the sometimes high promiscuity of transporters, often resulting in unpredictable outcomes. This review provides an overview of recent progress in transporter engineering and characterization methods, highlighting their potential to enhance the production of bio-based chemicals.
?'s insight:

1str

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December 20, 11:46 PM
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Principles for Rigorous Design and Application of Synthetic Microbial Communities | AdvS

Principles for Rigorous Design and Application of Synthetic Microbial Communities | AdvS | RMH | Scoop.it

Synthetic microbial communities (SynComs) are microbial consortia with defined taxonomic and functional traits, so that the combination elicits a predictable response under defined conditions. SynComs are artificially designed to enable inter-species metabolic interactions, metabolic division of labor, and ecological interactions that can elicit phenotypes like colonization stability and environmental adaptation. As an applied tool, SynComs have been deployed in diverse contexts, including agriculture, industry, and environmental ecology. This systematic review explores the processes used to construct SynComs, the mechanisms of metabolic interaction between members, and a review of the different ways that SynComs have been applied. We also explore the challenges for SynCom development and application, and future research directions that could overcome these challenges. SynComs are a powerful tool in our arsenal of applied technologies, but research and application are still nascent. While advances have been made, more research is needed to ensure SynCom technologies do not threaten global ecological security. SynCom technology represents a versatile platform for the controlled manipulation of microbial systems, enabling targeted modification of ecological and physiological processes. This emerging field marks a transition from descriptive biology toward a predictive and engineering-driven framework for understanding and shaping living systems.

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December 20, 11:33 PM
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Evolution and design shape protein dynamics in LOV domains – spanning picoseconds to days | jmb

Evolution and design shape protein dynamics in LOV domains – spanning picoseconds to days | jmb | RMH | Scoop.it

Light-sensitive proteins allow organisms to perceive and respond to their environment, and have diversified over billions of years. Among these, Light-Oxygen-Voltage (LOV) domains are widespread photosensors that control diverse physiological processes and are increasingly used in optogenetics. Yet, the evolutionary constraints that shaped their protein dynamics and thereby their functional diversity remain poorly resolved. Here we systematically characterize the dynamics of 21 natural LOV core domains, significantly extending the spectroscopically resolved catalog through the addition of 18 previously unstudied variants. Using time-resolved spectroscopy, we uncover an exceptional kinetic diversity spanning from picoseconds to days and identify distinct functional clusters within the LOV family. These clusters reflect evolutionary branching, including a divergence of  1.0 billion years between investigated LOV variants from plants and 0.4 billion years of separation within one of these functional clusters. Individual variants with extreme photocycles emerge as promising anchor points for optogenetic applications, ranging from highly efficient adduct formation to ultrafast recovery. Beyond natural diversity, we introduce a LOV domain generated by artificial intelligence-guided protein design. Despite being sequentially remote from its maternal template, this variant retains core photocycle function while exhibiting unique biophysical properties, thereby occupying a new region on the biophysical landscape. Our work emphasizes how billions of years of evolution defined LOV protein dynamics, and how protein design can expand this repertoire, engineering next-generation optogenetic tools.

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December 20, 11:26 PM
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Engineering the gut microbiome and its impact on human health | Cin

Engineering the gut microbiome and its impact on human health | Cin | RMH | Scoop.it
The gut microbiome plays a crucial role in maintaining health by supporting digestion, immunity, and overall well-being. Disruptions to the gut microbiome can result in dysbiosis, which is correlated with disease states. Recent advances in engineering the gut microbiome, functional ingredients designed through prebiotics, probiotics, and synbiotics have progressed together with synthetic microbial communities (SynComs), which influence the modulation of microbiome composition and functional role, offering a promising strategy to restore balance and enhance health. This field is rapidly advancing with broad applications focused on improving animal and human health. This review explores the significance and current applications of the engineering microbiome and its impact on gut health, as well as the challenges and sustainable future.
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December 20, 10:49 PM
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Machine learning enables scalable and systematic hierarchical virus taxonomy | Nbt

Machine learning enables scalable and systematic hierarchical virus taxonomy | Nbt | RMH | Scoop.it

Although virus ecogenomics has expanded access to and understanding of the virosphere, existing classification tools lack taxonomic resolution and are unable to scale to modern discovery-based datasets or classify previously unknown sequence space. Here we develop vConTACT3—a machine learning-based tool that improves scalability and accuracy of virus taxonomy. By optimizing gene-sharing thresholds and leveraging adaptive, realm-specific cut-offs, vConTACT3 expands classification to both eukaryote and prokaryote viruses for four of the six officially recognized realms, and establishes accurate hierarchical taxonomy from genus to order. Specifically, vConTACT3 achieves >95% agreement with official taxonomy for 35,545 and 13,524 public prokaryotic and eukaryotic virus genomes, respectively, to surpass vConTACT2 across most realms, while still uniquely classifying previously uncharacterized taxa, and doing so even faster. vConTACT3 application provides taxonomy assignments for tens of thousands of unclassified taxa rapidly, automatically and systematically; evaluates virus sequence space to reveal support for fewer taxonomic ranks than currently available and identifies taxonomically challenging areas across the virosphere. vConTACT3 enables multirank, large-scale classification of eukaryotic and prokaryotic viruses.

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An engineered multi-step differentiation program in Escherichia coli for self-organized spatial patterning | brvsb

An engineered multi-step differentiation program in Escherichia coli for self-organized spatial patterning | brvsb | RMH | Scoop.it

In nature, complex multicellular structures originate from individual cells containing all essential information for differentiation, patterning and morphogenesis. Synthetic biology enables a bottom-up approach to study these processes by engineering and combining individual modules to progressively increase the system's complexity. Here, we engineered a multi-step differentiation program in the model prokaryote E. coli. Starting from genetically identical cells and without providing any external positional information, we generated autonomous spatial patterns of colonies on a solid surface. We first employed a toggle switch to break population homogeneity (symmetry breaking), stochastically differentiating cells into two subpopulations: senders and receivers. Next, we enabled further differentiation of receiver colonies located in close proximity to sender colonies via quorum-sensing based communication (paracrine signaling). Finally, the newly emerged population matured into a different cell type via an orthogonal, self-activating, quorum sensing signal (autocrine signaling). The diversity of spatial patterns generated by this multi-step program was accurately captured by simulations of a corresponding mathematical model. Together, these results demonstrate that multi-step differentiation programs can be engineered in unicellular bacteria to drive fully self-organized spatial pattern formation.

?'s insight:

schaerli y, stem cell, 2st

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Resource ratio fluctuations drive the evolution of microbial metabolic strategies | brveco

Resource ratio fluctuations drive the evolution of microbial metabolic strategies | brveco | RMH | Scoop.it

Microorganisms employ diverse metabolic strategies to cope with environmental variability, yet the evolutionary conditions that favor specialists, hierarchical utilizers, or co-utilizers remain poorly understood. Here, we investigate how fluctuations in resource supply ratios drive the evolution of metabolic strategies. By simulating microbial community assembly in environments with variable resource ratios, we show that diverse metabolic strategies emerge as evolutionary optima in different fluctuation regimes. We find that environments with balanced resource supply select for specialists, whereas imbalanced environments select for generalists. As the magnitude of fluctuations in resource supply ratios progressively increases, generalist strategies smoothly shift from those of hierarchical utilizers to co-utilizers. We identify the duration of temporal niches as the mechanistic driver that selects for reduced lag times over maximal growth rates. These findings demonstrate how the temporal structure of resource availability can spontaneously generate the three distinct metabolic strategies observed in nature.

?'s insight:

microbial assembly

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Microbial engineering for sustainable microplastic biodegradation: from enzyme redesign to synthetic consortia

Microbial engineering for sustainable microplastic biodegradation: from enzyme redesign to synthetic consortia | RMH | Scoop.it

Microplastics are widely recognized as persistent and pervasive contaminants that endanger human health and ecosystems. Traditional remedial techniques are problematic due to high costs and inefficiency. One sustainable method of dissolving tough polymers into recyclable parts is through microbial and enzymatic engineering. Recent advances in genome-editing technologies, enzyme redesign, and synthetic biology particularly CRISPR-based systems have transformed the way we approach enhancing the efficiency of biodegradation. Recent CRISPR applications, such as base editing and promoter modification, have improved the stability and expression of enzymes, accelerating the catalytic activity of PET hydrolases, including PETase and cutinase. To enable scalable plastic biodegradation, this review combines hybrid CRISPR-based systems with microbial and enzyme engineering techniques. The goals of computational and machine learning–based enzyme design is thermostability and substrate adaptation, while hybrid microbial communities made up of modified bacteria and fungi improve degradation through cooperative processes. Furthermore, combining synthetic biology with hybrid remediation techniques, such as biofilm reactors and enzyme-nanoparticle conjugates, links laboratory research developments with real-world applications. However, issues remain regarding the scalability of polyethylene (PE) and polystyrene (PS) degradation, biosafety standards for genetically modified organisms (GMOs), and environmental hazards associated with degradation byproducts. To effectively manage plastic waste, future research should focus on creating thermostable enzymes, forming synthetic consortia guided by multi-omics, and developing safe hybrid bio-physical systems that support circular bio economy models.

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Today, 12:19 PM
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Computational design of allulose-responsive biosensor toolbox for auto-inducible protein expression and CRISPRi mediated dynamic metabolic regulation | Ncm

Computational design of allulose-responsive biosensor toolbox for auto-inducible protein expression and CRISPRi mediated dynamic metabolic regulation | Ncm | RMH | Scoop.it

Biosensors based on transcription factors (TFs) have shown extensive applications in synthetic biology. Due to the complex multi-domain structure of effector-TF-DNA, computational design of TFs remains a challenge. Here, we present the successful structure-guided computational design of the access tunnel, ligand binding, allosteric transition process for an allulose-responsive PsiR. It enables a 20-fold increase in sensitivity, reducing the EC50 of PsiR-allulose biosensors (PABs) from 16 mM to 0.8 mM, and delivers a PAB box possessing the detection range from 10 μM to 100 mM. We further validate its broader applicability in enhancing sensitivity of LacI-IPTG biosensor. Based on the developed PABs, we present the inducer-free allulose-mediated auto-inducible protein expression system, and demonstrate an allulose-triggered CRISPR interference circuit for dynamic metabolic regulation. It facilitates a 68% increase in allulose titer and achieves a high yield of 0.43 g/g glucose. This work provides the versatile TF toolbox for developing allulose-triggered regulation circuits in biotechnology application. Transcription-factor biosensors enable programmable metabolism. Here, the authors integrate structure and computation for mechanism-guided iterative redesign of the allulose biosensor PsiR, increasing sensitivity and dynamic range, enabling allulose-triggered expression system and CRISPRi circuit.

?'s insight:

2st, sensor, directed evolution, we prioritized the engineering of effector access (step i), reasoning that modifying allulose entry access is less likely to perturb the delicate intramolecular allosteric network. Based on the PsiR-allulose complex crystal structure, we analyzed the potential access tunnels using CAVER 3.0. Among the identified tunnels, the tunnel 1, comprising residues R109, V134, T135, D155, and D202, exhibited the widest bottleneck radius, lowest curvature, and highest flux, and was therefore considered the primary tunnel for inducer movement.  enhancement of allulose binding via a suitable conformation in the binding pocket would generate more robust triggering response ability.

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Maintenance of cytoplasmic and membrane densities shapes cellular geometry in Escherichia coli | Ncm

Maintenance of cytoplasmic and membrane densities shapes cellular geometry in Escherichia coli | Ncm | RMH | Scoop.it

Microbes precisely control their composition and geometry across diverse growth conditions, yet the mechanisms coordinating these processes remain unclear. Here, we integrate quantitative proteomics, microscopy, and biochemical measurements to reveal a biophysical principle linking these properties in Escherichia coli: cytoplasmic and membrane protein densities maintain a tightly conserved ratio across growth conditions, while the periplasmic density varies. Building on this observation, we develop a mathematical model demonstrating that maintaining this density ratio constrains the surface-to-volume ratio as a nonlinear function of proteome composition, specifically the ribosomal proteome fraction and partitioning between cellular compartments. The model holds under guanosine tetraphosphate perturbations that alter ribosome levels, further demonstrating that cellular geometry is not strictly determined by growth rate. These findings provide a biophysical framework for geometry control, underscoring density maintenance as a key physiological constraint that shapes cellular phenotypes. Chure et al. analyse experimental data to show that E. coli bacteria maintain stable protein density ratios between cytoplasm and membranes. In addition, they develop a biophysical model that predicts surface-to-volume ratio from ribosomal content and protein partitioning across cell compartments.

?'s insight:

2st,  show that the cytoplasmic and periplasmic proteome partitions are strongly anti-correlated, suggesting a trade-off in localization between these compartments, while the membrane fraction of the proteome is constant across growth conditions. Given these relations, we propose that the surface-to-volume ratio is controlled such that the macromolecular densities within these compartments are tightly constrained.

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December 21, 1:28 PM
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What do you most hope we will achieve with mammalian synthetic biology within the next decade? | csys

Over the next decade, mammalian synthetic biology should become the first precision control layer for human physiology. Synthetic gene circuits will sense molecules—glucose, lipids, and cytokines—and actuate closed-loop, real-time corrections integrated with host metabolism. This retires open-loop, Paracelsus-era dosing—pills at fixed intervals—in favor of continuous control. Placement should follow safety and access, not organ identity: subcutaneous sensing and control, by autologous cells, exosome/RNA cargoes, or xenogeneic tissue, and encapsulation or immune shielding manage risk. Metabolic control is modular—blood glucose does not need be controlled from the pancreas, nor do lipids need to be lowered by the liver. As circuits interface with metabolism, diagnosis, prevention, and therapy converge—shifting care from chronic management to cure.
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December 21, 1:01 PM
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Integrating protein language and geometric deep learning models for enhanced vaccine antigen prediction | Ncm

Integrating protein language and geometric deep learning models for enhanced vaccine antigen prediction | Ncm | RMH | Scoop.it

Vaccines are the most effective tool in preventing and managing infectious diseases. One of the critical challenges in vaccine development is the selection of suitable target antigens from the thousands of proteins produced by pathogens. Artificial intelligence is anticipated to play a significant role in addressing this challenge. In this study, we develop a framework termed PLGDL for protective antigen prediction that employs Protein Language and Geometric Deep Learning models. This framework leverages both primary sequence features and three-dimensional structural features of protein antigens, thereby reducing the biases associated with manually curated features. Our integrated model exhibits robustness across both constructed and public datasets and is applicable to viruses, bacteria, and eukaryotic pathogens. Notably, when applied to the ongoing Mpox outbreak, our model not only quickly identifies multiple known antigens but also discovers a protective antigen: G10R. Here, our study provides a high-performance screening tool for protective vaccine antigen prediction by synergistically utilizing the capabilities of protein language and geometric deep learning models, providing substantive insights and methodological advancements for rapid vaccine development. Vaccines are the most effective tool in managing infectious disease and characterizing features of protective epitopes could help in prediction methods. Here the authors use protein language and geometric deep learning frameworks to investigate primary sequence features and structural features to identify and predict potential antigens, showing prediction of a protective mpox epitope using this method.

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December 21, 12:29 PM
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Single cell profiling framework reveals metabolic subpopulations as drivers of bioproduction heterogeneity | Ncm

Single cell profiling framework reveals metabolic subpopulations as drivers of bioproduction heterogeneity | Ncm | RMH | Scoop.it

Heterogeneity within clonal cell populations remains a critical bottleneck within bioprocess engineering, notably by undermining bioproduction yields. Efforts to mitigate its impact have, however, been hampered by technological difficulties quantifying metabolism at the single-cell level. Here, we propose a framework based on single-cell biosensor analysis that enables robust characterization of cell’s metabolic states, leveraging it to detect and isolate isogeneic heterogeneity in response to environmental perturbations and within microbial cell factories. We identify acute and gradual glucose depletion to induce differentiation of metabolically distinct subpopulations and reveal these subpopulations to exhibit differential production capabilities, with lower intracellular pH subpopulations exhibiting enhanced product accumulation within violacein-producing strains but reduced yields within lycopene-producing strains. Lastly, we highlight galactose cultivation as a method to modulate subpopulation dynamics towards higher-producing lycopene phenotypes. Altogether, our research provides insights into subpopulation differentiation and establishes promising avenues for the engineering of more robust and higher-producing strains. Heterogeneity within clonal cell populations affects bioprocess engineering. Here, the authors report a biosensor-based toolkit to investigate phenotypic heterogeneity in engineered yeast, reveal pH-based subpopulations and metabolite production states, and modulate/shift subpopulation dynamics to increase lycopene production.

?'s insight:

2st, yeast. facs, ph sensor, pHi serves as a valuable indicator of cellular stress, with pHi homeostasis being vital to maintaining cellular function and transient drops in pHi often playing a crucial role in initiating cells’ stress responses. 

FBP is an intermediate of the glycolytic pathway whose abundance directly correlates with glycolytic flux, a core component of carbon metabolism41, while absolute ATP levels and the ratio of ATP:ADP are reflective of a cell’s energy status. Lastly, NAD+:NADH and NADP+:NADPH ratios determine the redox balance of cells which is critical in allowing many enzymatic reactions. 

we explored the potential of galactose as a carbon source to alleviate the burden imposed by p1 on lycopene production, by favoring differentiation to p2. Galactose-grown cells have been shown to display reduced overflow metabolism resulting in increased respiration levels frequency

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December 20, 11:56 PM
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Transcriptional profiling of Pseudomonas aeruginosa biofilm life cycle stages reveals dispersal-specific biomarkers | brvm

Transcriptional profiling of Pseudomonas aeruginosa biofilm life cycle stages reveals dispersal-specific biomarkers | brvm | RMH | Scoop.it

Bacteria exhibit two lifestyles: planktonic free-floating individual cells or sessile multicellular aggregates known as biofilms. The biofilm lifecycle is characterized by three distinct stages: attachment, maturation and dispersal. Specific signals govern each stage triggering responses that spatially and temporally regulate bacterial attachment to a surface, synthesis of extracellular matrix components and their subsequent degradation. Characterizing these signals is therefore a valuable approach to develop novel antibiofilm therapies. Here, we used the model biofilm-forming bacterium Pseudomonas aeruginosa PAO1 to characterize the transcriptional profiles of each stage of the biofilm life cycle: attachment, biofilm maturation and spontaneous dispersal. We report that surface attachment was accompanied by the upregulation of genes comprising the mechanosensor Pil-Chp, whereas biofilm maturation characterised with the upregulation of genes involved in Pel polysaccharide synthesis, siaD and PA4396 diguanylate cyclases as well as pipA, fimX and PA5442. In contrast, dispersing cells upregulated genes responsible for alginate, rhamnolipid, and extracellular nucleases (eddA, eddB) biosynthesis, as well as the transcriptional regulator of dispersal amrZ. Additionally, genes encoding the quorum sensing dispersal molecule cis-2-decenoic acid (dspS and dspI), canonical phosphodiesterases (nbdA and rbdA) and eleven other c-di-GMP–related enzymes were also upregulated during dispersal. Our comprehensive analysis of transcriptional profiles associated with different biofilm stages allowed us to define a subset of fourteen genes as biomarkers of biofilm dispersal. Our study therefore provides benchmarking stage-specific transcriptional profiles for P. aeruginosa biofilms in closed culture systems, which led to the identification of a dispersal fingerprint marking the onset of dispersal.

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December 20, 11:33 PM
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The changing roles of Escherichia coli | Nmb

The changing roles of Escherichia coli | Nmb | RMH | Scoop.it

Richard Lenski traces the legacy of Escherichia coli and how science is evolving to use this model organism in new ways.

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December 20, 11:30 PM
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Detection of Spoilage-Associated Acetic Acid Levels Using a Transcription-Based Whole-Cell Biosensor | mbt

Detection of Spoilage-Associated Acetic Acid Levels Using a Transcription-Based Whole-Cell Biosensor | mbt | RMH | Scoop.it

Monitoring acetic acid (AC) in fermentation processes is essential as excessive AC accumulation, particularly during alcoholic fermentation, can disrupt fermentation and lead to spoilage. However, conventional detection methods such as steam distillation, GC–MS, and HPLC are costly, time-consuming, and require liquid-phase samples, limiting their use for real-time monitoring and early identification of AC buildup. Here, we present an alternative tool for AC detection using a whole-cell bacterial biosensor, which utilizes the YwbIR transcriptional regulator from Bacillus subtilis. The designed biosensor exhibits high sensitivity, manifesting a linear response with (R2 = 0.97) from 0 to 1.0 g/L and a 5–8 fold induction at wine spoilage-relevant concentrations. It retains functionality in ethanol-rich matrices (up to 14.5% v/v) and enables headspace detection. Specificity assays and molecular docking analyses confirm high affinity for AC over other volatile fatty acids. This biosensor offers a low-cost solution for real-time AC monitoring, allowing timely intervention before spoilage occurs and supporting improved quality assurance in fermentation-driven food and beverage production.

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December 20, 11:25 PM
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A guide to designing cell-surface receptors in plants | Cin

A guide to designing cell-surface receptors in plants | Cin | RMH | Scoop.it
Cell-surface receptors perceive environmental cues and trigger appropriate responses. In plants, these receptors comprise ectodomain, juxta-membrane, and cytosolic regions that define ligand specificity, modulate co-receptor associations, and fine-tune downstream signaling, respectively. Here we highlight the mechanistic principles underlying each module and discuss strategies to reprogram them. By integrating structural insights with illustrative examples, we provide a blueprint for designing cell-surface receptors with customized recognition specificity and programmable outputs, offering new opportunities to enhance plant resilience in the face of rapid climate change.
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