PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Synthetic biology”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2026

Biological Parts in Yeast Synthetic Biology: From Regulatory Elements to Predictive Design Platforms.

Yeasts, particularly Saccharomyces cerevisiae, are important eukaryotic chassis for synthetic biology because of their tractable genetics, versatile toolkits, and broad utility in metabolic engineering and functional genomics. Progress in this field has been driven by biological parts that enable programmable control of gene expression and cellular behavior. Early efforts focused mainly on promoters, terminators, and other regulatory elements for tuning individual genes. However, as engineering expanded to multigene pathways, genetic circuits, and dynamic regulatory systems, the limits of part-centric design became clear. Part performance is often shaped by genomic context, chromatin state, host physiology, and interactions with other components, which restricts modularity and predictability. In response, yeast synthetic biology is shifting toward integrated design frameworks combining multilayer regulation, standardized assembly, automated experimentation, and computational modeling. This review provides an integrated perspective on the evolution of biological parts across DNA-, RNA-, and protein-level regulation, connecting these advances with assembly frameworks, biofoundries, and machine learning to trace the trajectory from part-centric engineering toward predictive, system-level design in yeast synthetic biology.

Biofoundry↗
PubMed1977

Renal effects of native parathyroid hormone and synthetic biologically active fragments in pseudohypoparathyroidism and hypoparathyroidism.

To gain further insight into the biological significance of parathyroid hormone (PTH) metabolism, native parathyroid hormone and synthetic peptides, similar to PTH metabolites generated in vivo, have been given intravenously to human subjects. The resultant changes in renal excretion of adenosine 6':5' monophosphate (cyclic AMP) and inorganic phosphate have been measured in five pseudohypoparathyroid, four hypoparathyroid, and one pseudopseudohypoparathyroid patient. As anticipated, native PTH promptly increased urinary cyclic AMP and phosphate excretion in the hypoparathyroid and pseudo-pseudohypoparathyroid patients, and had little or no effect on their excretion in the pseudohypoparathyroid patients. Synthetic bovine parathyroid hormone 1-34 and synthetic human parathyroid hormone 1-34 had effects essentially identical to each other and to native PTH. We conclude that the PTH resistance of pseudohypoparathyroidism is probably not caused by a defect in PTH metabolism. We further conclude that synthetic human or bovine parathyroid hormone 1-34 could be used for diagnostic evaluation of patients.

Creatinine↗
PubMed2026

A Comprehensive Review on the Biosynthesis of Tropane Alkaloids.

Tropane alkaloids (TA) constitute a class of plant specialized metabolites with important pharmaceutical applications, including the anticholinergic agents hyoscyamine and scopolamine and the local anesthetic cocaine. Over the past decade, advances in genomics, structural biology, and synthetic biology have substantially revised our understanding of TA biosynthesis, leading to the identification of numerous key biosynthetic enzymes and evolutionary mechanisms. This review comprehensively summarizes current knowledge of TA biosynthesis from precursor formation to structurally diverse end products. We describe the pathway from putrescine to tropinone, the stereoselective metabolic branching mediated by Tropinone Reductases, and the downstream biosynthesis of medicinal tropane alkaloids, calystegines, and cocaine. Particular emphasis is placed on recent discoveries concerning catalytic mechanisms, structural determinants of substrate specificity, metabolic compartmentalization, and the convergent evolution of TA biosynthesis in Solanaceae and Erythroxylaceae. We further integrate advances in genomics, evolutionary biology, and metabolic engineering to highlight emerging strategies for microbial production and pathway redesign. By providing a comprehensive synthesis of recent progress and critical perspectives on unresolved questions, this review offers an updated framework for understanding TA biosynthesis and supports future research in plant specialized metabolism, synthetic biology, and natural product engineering.

Tropanes↗
PubMed1977

Association of macrophage activation with antitumor activity by synthetic and biological agents.

Treatment of normal BALB/c mice i.p. with a number of adjuvants, including pyran copolymer, the copolymer of polyinosinic and polycytidylic acids, Bacillus Calmette-Guérin, glucan, and dextran sulfate, rendered macrophages nonspecifically cytostatic for syngeneic tumor cells. Macrophage activation was highly dose dependent. The validity of the inhibition of DNA synthesis assay for measuring macrophage-induced cytostasis of target cells was proven by demonstrating a concurrent decrease in RNA synthesis and a reduction in viable tumor cell number. Moreover, conditioned supernatants from pyran-activated macrophages did not significantly decrease [3H]thymidine incorporation by freshly added leukemia cells. Biological or synthetic agents that activated macrophages were generally effective systemic antitumor agents against the M109 lung carcinoma. Drugs that did not activate macrophages, such as typhoid vaccine, tilorone, levamisole, WY-13876, and thymosin, were ineffective in prolonging the life of tumor-bearing mice. Pyran treatment i.p. was the most effective antitumor adjuvant in two separate tumor models, and suppression of tumor growth appeared to be related not only to an increase in macrophage tumoricidal function, but also to a larger influx of macrophages responding at the tumor site.

Animals↗
PubMed2026

Application of emerging technologies in the antiviral field.

Viral diseases pose a serious threat to global public health, agriculture, and biosecurity. Conventional antiviral strategies are often limited by an incomplete understanding of disease mechanisms, poor targeting precision, and slow response times. Emerging technologies are now reshaping the landscape of antiviral research. This review examines the roles of four key frontiers, including organoid models, gene editing, AI-driven molecular design, and synthetic biology. Organoids provide physiologically relevant platforms that model virus-host interactions and disease progression. Viral infections remain a major challenge to human and animal health, agriculture, and biosecurity. Progress in antiviral research is constrained by the complexity of viral pathogenesis, the diversity and rapid evolution of viruses, and the limited translational relevance of some traditional model systems. Recent advances in organoid technology, gene editing, artificial intelligence, and synthetic biology are expanding the toolkit available for antiviral research and development. In this review, we discuss how these four technological frontiers contribute to disease modeling, target discovery, molecular design, and translational innovation. Organoids, in particular, provide physiologically relevant systems for investigating viral infection, tissue tropism, host responses, and pathogenesis. Gene editing tools, such as CRISPR, enable precise manipulation of host and viral genomes, facilitating the development of resistant organisms and next-generation vaccine platforms. AI technologies, including AlphaFold for structure prediction and platforms for de novo protein design, address long-standing bottlenecks in structural biology and offer powerful means to engineer antiviral proteins, antibodies, and vaccine antigens. Synthetic biology, guided by the Design-Build-Test-Learn cycle, integrates computational design, genetic assembly, and functional validation into a cohesive pipeline. Together, these technologies form a synergistic workflow that spans disease modeling, target discovery, molecular design, construction, testing, and iterative optimization. This integrated approach is shifting antiviral development from traditional empirical methods toward more precise, intelligent strategies. The review also highlights ongoing challenges in integration and scalability, stressing that high-quality biological datasets and stronger interdisciplinary collaboration are essential for realizing translational potential. By presenting a cohesive view of these converging methodologies, this review offers a framework to guide the intelligent evolution of antiviral strategies in both human and animal health.

Antiviral↗
PubMed2025

FluxRETAP: a REaction TArget Prioritization genome-scale modeling technique for selecting genetic targets.

MOTIVATION: Metabolic engineering is rapidly evolving as a result of new advances in synthetic biology tools and automation platforms that enable high throughput strain construction, as well as the development of machine learning tools (ML) for biology. However, selecting genetic engineering targets that effectively guide the metabolic engineering process is still challenging. ML can provide predictive power for synthetic biology, but current technical limitations prevent the independent use of ML approaches without previous biological knowledge. RESULTS: Here, we present FluxRETAP, a simple and computationally inexpensive method that leverages the prior mechanistic knowledge embedded in genome-scale models for suggesting targets for genetic overexpression, downregulation or deletion, with the final goal of increasing the production of a desired metabolite. This method can provide a list of desirable engineering targets that can be combined with current ML pipelines. FluxRETAP captured 100% of reaction targets experimentally verified to improve Escherichia coli isoprenol production, 50% of targets that experimentally improved taxadiene production in E. coli and ∼60% of genetic targets from a verified minimal constrained cut-set in Pseudomonas putida, while providing additional high priority targets that could be tested. Overall, FluxRETAP is an efficient algorithm for identifying a prioritized list of testable genetic and reaction targets. AVAILABILITY AND IMPLEMENTATION: FluxRETAP is implemented in python and released under the creative commons license. The implementation and code are freely available at: https://github.com/JBEI/FluxRETAP.

Escherichia coli↗
PubMed2026

CREAT: A CRISPR-Based Genome Trimming Strategy for Systematic Identification of Dispensable Regions and Rapid Genome Reduction.

The construction of minimal-genome microbes offers an ideal platform for understanding fundamental biological processes and synthetic biology, yet the research is hindered by incomplete lists of essential genes in microbes and by multiple rounds of genome trimming with a trial-and-error nature. To address this, we introduce CREAT (CRISPR-based genome trimming with a multi-homology-arm template)-a streamlined approach that integrates CRISPR-targeted genome cleavage and homology arm walking to classify essential from non-essential genomic subregions, thus providing the basis for predicting essential genes in a given organism. These essential genes were then assembled into synthetic gene cassettes for one-step replacement of the targeted non-deletable genomic regions for further genome trimming. Eight consecutive rounds of CREAT genome trimming achieved a 20.8% reduction in genome size in Saccharolobus islandicus. Furthermore, Cas9-based CREAT genome trimming was developed for Bacillus subtilis and Escherichia coli, with efficiency greatly enhanced by the λ-Red recombinase in the latter. Together, this iterative application of CREAT provides a scalable and generally applicable strategy for rapidly constructing minimal genomes across diverse microorganisms.

CRISPR-Cas Systems↗
PubMed2026

Modular synthetic cross-kingdom promoters enable coordinated expression in Escherichia coli and Saccharomyces cerevisiae.

Synthetic biology and metabolic engineering increasingly demand predictable and interoperable gene expression across phylogenetically distant organisms, as the need for portable genetic systems and transferable metabolic pathways continues to grow. However, fundamental differences in promoter architecture and transcriptional logic across kingdoms remain a key bottleneck in developing universal expression platforms. Here, we designed a set of modular hybrid promoters that enable tunable and quantitatively consistent gene expression in both Escherichia coli and Saccharomyces cerevisiae. These promoters integrate bacterial -10/-35 motifs and Shine-Dalgarno sequences with minimal yeast TATA boxes and Kozak sequences to ensure transcriptional and translational compatibility. The promoter set supported weak, moderate, and strong expression with high relative consistency across species. Applied to the biosynthetic pathway for the valuable pigment prodeoxyviolacein, the hybrid promoters enabled coordinated production in both hosts. This work establishes a broadly compatible promoter architecture and provides a foundational toolkit for cross-kingdom, multi-host synthetic biology.

Promoter Regions, Genetic↗
PubMed2026

Host-aware Identification of Intrinsic Gene Expression Biopart Parameters using Combinatorial Libraries.

Model-based design in synthetic biology is limited because bioparts are typically characterised by relative metrics that vary across genetic and physiological contexts. To address this, we introduce a host-aware framework for quantitatively characterising bioparts in combinatorial libraries of plasmid-based constitutive expression constructs. The approach integrates a digital twin of Escherichia coli, conditioned on measured growth rate, with model-in-the-loop parameter identification to separate biopart-associated properties from host-dependent effects. Using structured combinatorial libraries, we identify mechanistically interpretable, transferable parameters for plasmid origins, promoters and ribosome binding sites. In particular, we define an intrinsic translation initiation capacity that captures the dominant RBS-associated contribution to translation while context-dependent expression emerges from host physiology and local sequence context. The resulting parameterisation accurately predicts protein synthesis across physiological conditions, supports incremental library expansion, and reveals localised failures of modularity, providing a scalable foundation for predictive host-aware design in synthetic biology.

Escherichia coli↗
PubMed2025

Efficient site-specific integration of kilobase-length DNA fragments in plant cells via Kp03 recombinase.

Targeted insertion of large DNA sequences into plant genomes remains a major challenge in synthetic biology. Here, we evaluate the large serine recombinase Kp03 for site-specific integration of DNA fragments in rice and Arabidopsis. In transient protoplast assays, Kp03 mediates efficient insertion of donor DNA up to 27.3 kilobases (kb), with plasmid integration efficiencies reaching 99.1% for fragments up to 3.4 kb. Truncation experiments reveal that a minimal 15-bp attB sequence is necessary for integration. As a proof of concept, Kp03 successfully incorporates a 3.4-kb donor DNA into the rice genome at a locus containing this minimal attB sequence. Moreover, in rice callus, combining Kp03 with the NM-PE genome editing system to install a 26-bp attB site enables targeted integration of a 3.4-kb donor at the desired genomic locus. These findings establish Kp03 as a versatile tool for plant genome engineering, with broad applications for synthetic biology.

Oryza↗
PubMed2026

Synthetic transcriptional repression systems in plants.

Transcriptional repression is a fundamental regulatory mechanism that enables precise control of gene expression in response to developmental signals and environmental stimuli. Synthetic biology can leverage this process within plants to engineer programmable transgene repression systems. This review examines strategies for harnessing prokaryotic repressors in eukaryotic systems to develop synthetic repression systems in plants. These systems utilize modular promoter and repressor architectures that can be tuned through operator placement and repression-domain fusion, respectively, to adjust transcriptional regulation. Chemically dependent inducibility can also be introduced either through use of native derepression mechanisms of the prokaryotic repressors or the incorporation of ligand-binding domains. Finally, this review explores key challenges in designing synthetic repression systems, including kinetics constraints, balancing ON and OFF states, and differences between transient and transgenic expression contexts. Overall, this review highlights modular design frameworks for tunable transgene expression in plants.

Gene Expression Regulation, Plant↗
PubMed1977

Biological activity of synthetic human insulin.

The biological activity of human insulin, prepared by total chemical synthesis, was compared in various tests in vivo and in vitro with that of natural human or pork insulin. The potencies of the synthetic and natural hormone, as determined by the mouse convulsion assay, by hypoglycaemic effect and diaphragm glycogen increase in fasted rats in vivo, or by stimulation of 14C-glucose metabolism in fat cells and binding to anti-insulin serum in vitro, did not differ significantly. It is concluded that this synthetic human insulin is biologically equivalent to the natural hormone.

Adipose Tissue↗
PubMed2026

Bacterial R-bodies with common morphologies and unrolling dynamics are phylogenetically scattered, indicating extensive lateral gene transfer and wide application potential.

Refractile bodies (R-bodies) of gram-negative bacteria are large proteinaceous assemblies, rolled up in the form of an Archimedean spiral. They exhibit rapid rod-like reversible extension in the micrometer range when cued by chemical environmental triggers and have potential for synthetic biology and biochip applications. Initially described for the Paramecium endosymbionts Caedibacter taeniospiralis and Caedimonas varicaedens, R-bodies have since been discovered in many classes of Pseudomonadota, both in endosymbionts and in non-endosymbionts. However, despite the fact that the genetics and morphologies, as well as the unrolling kinetics of R-bodies from different species, show considerable diversity, no recent study has integrated these aspects into a single framework. The latter would be advantageous for the creation of an R-body biotechnology toolbox, where different properties determine the application area. Here, we have examined the R-bodies from six different Pseudomonadota, comprising both phylogenetically diverse endosymbionts and non-endosymbionts. Comparison of the morphologies of the rolled-up and unrolled forms, obtained using electron microscopy and high-quality images, to their corresponding genetic data indicates that extensive lateral gene transfer has occurred, which confounds a common framework based on these data. However, we have also studied the R-body extension and retraction kinetics using high frame-rate light microscopic video recordings, where we show for the first time that R-bodies can be classified into two classes, showing "fast burst" or "slow" acid-induced extension kinetics, respectively. We propose that this criterion may, in fact, be the most useful for the choice of an R-body tool for biotechnological purposes.IMPORTANCER-bodies are unique proteinaceous macromolecular structures capable of massive reversible extension in response to external environmental triggers without the input of chemical energy. They comprise only a few small polypeptides, which makes them potentially highly amenable to tuning via genetic engineering, as well as being exceptionally stable. These properties would be highly desirable in biotechnology and synthetic biology, as well as in biochip applications, where a controlled mechanical extensor might play an integral part in a nanoscale molecular machine. So far, only R-bodies from a single species, Caedibacter taeniospiralis, have been characterized extensively. However, in recent years, genomic information has revealed that a panoply of R-bodies are widely distributed among gram-negative phyla, although studies have generally not included morphological data. This study brings these two areas together to provide a holistic overview of the field and also reveals new insights into key dynamic aspects of R-body extension.

R-bodies↗
PubMed2025

Analog epigenetic memory revealed by targeted chromatin editing.

Cells store information by means of chromatin modifications that persist through cell divisions and can hold gene expression silenced over generations. However, how these modifications may maintain other gene expression states has remained unclear. This study shows that chromatin modifications can maintain a wide range of gene expression levels over time, thus uncovering analog epigenetic memory. By engineering a genomic reporter and epigenetic effectors, we tracked the gene expression dynamics following targeted perturbations to the chromatin state. We found that distinct grades of DNA methylation led to corresponding, persistent gene expression levels. Altering the DNA methylation grade, in turn, resulted in permanent loss of gene expression memory. Consistent with experiments, our chromatin modification model indicates that analog memory arises when the positive feedback between DNA methylation and repressive histone modifications is lacking. This discovery will lead to a deeper understanding of epigenetic memory and to new tools for synthetic biology.

Epigenesis, Genetic↗