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Analysis of myxobacterial secondary metabolism goes molecular.

During the last 20 years myxobacteria have made their way from highly exotic organisms to one of the major sources of microbial secondary metabolites besides actinomycetes and fungi. The pharmaceutical interest in these peculiar prokaryotes lies in their ability to produce a variety of structurally unique compounds and/or metabolites with rare biological activities. This review deals with the recent progress toward a better understanding of the biology, the genetics, the biochemistry and the regulation of secondary metabolite biosynthesis in myxobacteria. These research efforts paved the way to sophisticated in vitro studies and to the heterologous expression of complete biosynthetic pathways in conjunction with their targeted manipulation. The progress made is a prerequisite for using the vast resource of myxobacterial diversity regarding secondary metabolism more efficiently in the future.

Gene Expression Regulation, Bacterial↗

Microbial diversity: the essential foundation for life on our planet.

The biological basis of life on Earth is microbial diversity that ensures human health, agricultural productivity, ecological balance, and ecosystem functioning. Microorganisms enable ecosystem restoration through bioremediation, maintain soil fertility, support plant growth, manage vital biogeochemical cycles, and contribute to climate resilience. Precision probiotics, postbiotics, faecal microbiota transplantation, and personalized microbiome medicine are the examples of emerging microbiome-based therapies that offer promising therapeutic opportunities. In humans, the gut microbial community is essential for immune regulation, metabolism, and disease prevention. In terrestrial ecological systems, interactions between plants, fungi, bacteria, and other soil microorganisms improve carbon sequestration, nutrient cycling, stress resilience, and sustainable agricultural productivity in the given effects of climate change. Emerging uses in agriculture, environmental restoration, and medicine are made possible by advancements in multi-omic techniques, synthetic microbial genomes, microbiome engineering, and artificial intelligence. Considering these developments, issues with ecological complexity, long-term validation, standardization, and field scale application still exist. Therefore, preserving microbial diversity is important for conserving ecological resilience and strengthening the One Health framework, which highlights the mutual dependance of health of animal, human, plant, and environment. This review summarizes what has been discovered about ecological and biomedical relevance of microbiome, identifies important research gaps, highlighting emerging technologies, and evaluates potential future directions for using microbiome to support planetary sustainability.

Bioremediation↗

Immunological identification of Tacaribe virus proteins.

Tacaribe virus (TV), an arenavirus, is an enveloped virus with genetic information encoded in two segments of single-stranded RNA. The completed sequence of TV led to the identification of four open reading frames (ORF). In order to establish a direct link between ORFs in the sequence of TV and proteins present in virus particles and virus-infected cells, segments of the molecularly cloned TV genome were engineered so as to be expressed in Escherichia coli to produce fusion proteins that were used to raise antisera. The antisera were in turn employed to identify the TV gene products. Serum to the putative nucleocapsid (N) protein reacted with a 68-kDa protein, both in TV particles and in the infected cells. Sera raised to the glycoprotein precursor (GPC) immunoprecipitated two proteins of 68 and 70 kDa from infected cell lysates. Analysis of GPC synthesis in the presence of tunicamycin revealed that the unglycosylated GPC appeared as two polypeptides of 43 and 46 kDa. The putative RNA polymerase gene product (L) was detected as a approximately 240-kDa protein. Serum to the small zinc-binding domain protein (p11-Z) recognized a protein of approximately 11kDa. Immunological evidence is presented that in addition to N and L, two glycoproteins (GP1 and GP2) and p11-Z are structural components of Tacaribe virions.

Animals↗

Microbial decaprenoxanthin: From understanding an extremophile-derived C50 carotenoid to its bioprocessing for large-scale applications.

Decaprenoxanthin (DPXT) is an unusual bacterial C50 carotenoid that has historically received limited attention despite its well-defined structure. For decades, carotenoid research and industrial development have been dominated by C40 carotenoids, leaving longer-chain carotenoids largely overlooked. Recent discoveries, particularly from microorganisms inhabiting Antarctic and other extreme environments, have repositioned DPXT as an adaptive pigment shaped by intense environmental pressures. Its extended polyene chain and membrane-associated behavior suggest roles in membrane stabilization and protection against ultraviolet radiation and oxidative stress, features that may hold relevance for food and biotechnological applications. This review integrates historical and recent knowledge on DPXT, covering its structural characteristics, biosynthetic pathways, ecological function, and emerging technological relevance. Special attention is given to microbial sources, particularly Actinomycetota from extreme environments, and to recent advances in microbial genomics, metabolic engineering, and sustainable bioprocess development that enable the production and exploration of C50 carotenoids beyond their native extremophilic context. The analysis highlights DPXT as a representative example of stress-resilient carotenoids, with physicochemical and membrane-interacting properties that may offer advantages for future food and biotechnological systems. Although significant challenges remain in cultivation strategies, yield optimization, and downstream recovery, advances in microbial cell factories and green extraction technologies open new opportunities for valorizing C50 carotenoids. This review bridges extremophile microbiology, carotenoid biochemistry, and sustainable food innovation, positioning DPXT as an emerging molecule that may expand the functional and structural landscape of carotenoids relevant to food science.

Carotenoids↗

Replication of the hepatitis C virus in cell culture.

Studies of hepatitis C virus (HCV) replication in cell culture have been greatly facilitated by the development of genetically engineered viral genomes that are capable of self-amplifying to high levels in a human hepatoma cell line. Since the original description of this 'replicon' model in 1999, important improvements have been made. Most notably, cell culture adaptive mutations were identified in various non-structural proteins that enhance RNA replication by several orders of magnitude. More recently, the permissiveness of the host cell was determined as an additional important factor contributing to efficient RNA replication. These discoveries allowed the development of transient replication assays, selectable full length genomes and a variety of novel replicons that will be useful for basic studies and facilitate the development of antiviral drugs. Ultimately, the replicon system may help to decipher the molecular basis of interferon-alpha (IFN-alpha) resistance.

Adaptation, Biological↗

Synonymous codon usage and gene function are strongly related in Oryza sativa.

The relationship between codon usage and gene function was investigated while considering a dataset of 2106 nuclear genes of Oryza sativa. The results of standard chi(2) test and F-statistic showed that for every 59 synonymous codons, a strongly significant association with gene functional categories existed in rice, indicating that codon usage was generally coordinated with gene function whether it was at the level of individual amino acids or at the level of nucleotides. However, it could not be directly said that the use of every codons differed significantly between any two functional categories. Notably, there existed large difference both in selection for biased codons or selection intensity among functional categories. Therefore, we identified at least two classes of genes: one group of genes, mainly belonging to the "METABOLISM" category, was tended to use G- and/or C-ending codons while the other was more biased to choose codons ending with A and/or U. The latter group contained genes of various functions, especially those genes classified into the "Nuclear Structure" category. These observations will be more important for molecular genetic engineering and genome functional annotation.

Chromosome Mapping↗

Genetic parts to program bacteria.

Genetic engineering is entering a new era, where microorganisms can be programmed using synthetic constructs of DNA encoding logic and operational commands. A toolbox of modular genetic parts is being developed, comprised of cell-based environmental sensors and genetic circuits. Systems have already been designed to be interconnected with each other and interfaced with the control of cellular processes. Engineering theory will provide a predictive framework to design operational multicomponent systems. On the basis of these developments, increasingly complex cellular machines are being constructed to build specialty chemicals, weave biomaterials, and to deliver therapeutics.

Bacteria↗

Towards mechanistic models of mutational effects: Deep learning on Alzheimer's Aβ peptide.

Deep Mutational Scanning (DMS) has enabled multiplexed measurement of mutational effects on protein properties, including kinematics and self-organization, with unprecedented resolution. However, potential bottlenecks of DMS characterization include experimental design, data quality, and depth of mutational coverage. Here, we apply deep learning to comprehensively model the mutational effect of the Alzheimer's Disease associated peptide Aβ42 on aggregation-related biochemical traits from DMS measurements. Among tested neural network architectures, Convolutional Neural Networks and Recurrent Neural Networks are found to be the most cost-effective models with high performance even under insufficiently-sampled DMS studies. While sequence features are essential for satisfactory prediction from neural networks, geometric-structural features further enhance the prediction performance. Notably, we demonstrate how mechanistic insights into phenotype may be extracted from the neural networks themselves suitably designed. This methodological benefit is particularly relevant for biochemical systems displaying a strong coupling between structure and phenotype such as the conformation of Aβ42 aggregate and nucleation, as shown here using a Graph Convolutional Neural Network (GCN) developed from the protein atomic structure input. In addition to accurate imputation of missing values (which here ranged up to 55% of all phenotype values at key residues), the mutationally-defined nucleation phenotype generated from a GCN shows improved resolution for identifying known disease-causing mutations relative to the original DMS phenotype. Our study suggests that neural network derived sequence-phenotype mapping can be exploited not only to provide direct support for protein engineering or genome editing but also to facilitate therapeutic design with the gained perspectives from biological modeling.

Alzheimer's disease↗

Epigenes: design and construction of new hereditary units.

A plasmid digene construction designed before [Tchuraev, R.N. (1982) J. Gen. Biol. 43, 79-87] has been realised, including feedback by repressing proteins with given trigger regime of gene functioning. Experimental tests of the expected epigene properties of the obtained pECPI recombinant plasmid involving lacI and cI(857) regulatory genes have shown a phenomenon of steady inheritance of two alternative epigenotypes lacI(1)cI(0) and lacI(0)cI(1), as well as an external toggle switch through metabolitic and temperature signals from one inherited functional state of the cyclic digene system into another. Thus, we have constructed a hereditary unit of a specific kind, namely, a two-component stationary epigene with preset properties.

Bacterial Proteins↗

Rhesus monkey rhadinovirus (RRV): construction of a RRV-GFP recombinant virus and development of assays to assess viral replication.

Rhesus monkey rhadinovirus (RRV) is a gamma-2-herpesvirus that is closely related to Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8). Lack of an efficient culture system to grow high titers of virus, and the lack of an in vivo animal model system, has hampered the study of KSHV replication and pathogenesis. RRV is capable of replicating to high titers on fibroblasts, thus facilitating the construction of recombinant rhadinoviruses. In addition, the ability to experimentally infect naïve rhesus macaques with RRV makes it an excellent model system to study gamma-herpesvirus replication. Our study describes, for the first time, the construction of a GFP-expressing RRV recombinant virus using a traditional homologous recombination strategy. We have also developed two new methods for determining viral titers of RRV including a traditional viral plaque assay and a quantitative real-time PCR assay. We have compared the replication of wild-type RRV with that of the RRV-GFP recombinant virus in one-step growth curves. We have also measured the sensitivity of RRV to a small panel of antiviral drugs. The development of both the recombination strategy and the viral quantitation assays for RRV will lay the foundation for future studies to evaluate the contribution of individual genes to viral replication both in vitro and in vivo.

Animals↗

Genetically tailored grapevines for the wine industry.

Grapevine biotechnology is one of the most promising developments in the global wine industry, which is increasingly faced with conflicting demands from markets, consumers and environmentalists. In the grapevine industries, this technology and its supporting disciplines entail the establishment of stress tolerant and disease resistant varieties of Vitis vinifera, with increased productivity, efficiency, sustainability and environmental friendliness, especially regarding improved pest and disease control, water use efficiency and grape quality. The implementation and successful commercialisation of genetically improved grapevine varieties will only be realized if an array of hurdles, both scientific and otherwise, can be overcome.

Biotechnology↗

From human genes to stem cells: new challenges for patent law?

The social controversies that have surrounded human cloning and the use of embryos for research purposes might create unique patent issues for stem cell researchers. Policy makers should learn from the legal and ethical concerns associated with human gene patents and develop coherent patent policies that recognize and clearly address emerging social controversies.

Canada↗

Engineering radiation-resistant bacteria for environmental biotechnology.

Seventy million cubic meters of ground and three trillion liters of groundwater have been contaminated by leaking radioactive waste generated in the United States during the Cold War. A cleanup technology is being developed based on the radiation-resistant bacterium Deinococcus radiodurans, which is being engineered to express bioremediating functions.

Bacteria↗