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Qiao and Nguyen et al. describe a strategy to block hypoxia-dependent gene expression in cell and mouse models of breast cancer through dual targeting of X-box-binding protein 1 and hypoxia-inducible factor binding to DNA with fully synthetic, stabilized artificial transcription factors.
Cao et al. introduce artificial lncRNA (alncRNA) for targeted protein degradation by engineering and linking lncRNA HOTAIR sequence to RNA aptamers. The resulting alncRNAs degrade oncogenic proteins, such as c-MYC and KRAS, showing promise for cancer therapies.
Pan et al. establish a general photoproximity labeling approach in living cells, applying microenvironment mapping with a HaloTag-based platform (HaloMap) to profile the stress granule proteome and identify ubiquitin-related modulators as key mediators of granule disassembly.
Organisms regulate biogenic crystal properties for various functions. Here the authors reveal the genetic and biochemical control of crystal morphogenesis in zebrafish iridophores, showing that the chemical composition, influenced by enzyme expression, determines crystal morphology and functionality.
Engineered demethylase LSD1 opens a new avenue in developing tools to study intricate relationships between histone post-translational modifications that can be enzymatically edited.
A method called massively parallel PPI measurement by sequencing (MP3-seq) is developed for measuring protein–protein interactions at scale. MP3-seq uses DNA barcodes that are associated with specific protein pairs and provides a quantitative measure of interaction strength. Interactions between rationally designed heterodimers and elements conferring interaction specificity were investigated using MP3-seq.
Assembly-line polyketide synthases perform modular enzymatic synthesis of medically important natural products. In this study, the authors used site-selective crosslinking to probe structural states that reveal how substrate carrier proteins interact with successive modules in a representative assembly line.
Spores harboring the gene circuit for the secretory expression of Burkholderia cepacia lipase were processed with poly(caprolactone) pellets to manufacture living plastics. Spore incorporation did not compromise the properties of the materials. Damage to the plastic surface and triggering of germinated cells caused secretion of the lipase, leading to depolymerization.
Boron is a common element found in various minerals; however, it is not used in life-creating machinery in nature. In a new study, boron enzymes have been created by introducing a boronic acid-containing non-canonical amino acid into an artificial enzyme scaffold. Further development via directed evolution enabled the selection of new-to-nature stereoselective chemistry.
Xiao et al. characterize 19 previously unidentified IscB proteins, 10 of which show activity in mammalian cells. They engineer one of the proteins into a robust in vivo genome-editing tool with a broad target-adjacent motif scope and further develop it into a base editor.
Understanding the physiological effects of antibiotics on bacterial cells is important for informing antibiotic use. Bacterial communities treated with antibiotics in a microfluidic device maintain glucose consumption at the community periphery, protecting interior cells from the effects of antibiotics.
Dynamic metabolic signatures underpin B cell function throughout development, maturation and differentiation. Germinal center B cells rely on MTHFD2-driven one-carbon metabolism that is dependent on antioxidant availability, purine synthesis and mTORC1 signaling.
A metabolic system of engineered biocatalysts using the noncanonical cofactor nicotinamide mononucleotide is established for biomanufacturing in cell-free systems and in Escherichia coli without interference from nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate.
Community-living promotes bacterial adaptation to antibiotics, allowing persistent glucose consumption and maintenance of spatial heterogeneity in the community, ensuring rapid recovery of the community postantibiotic treatment.
Profiling endogenous Ras (rat sarcoma virus) activity during Ras-G12C inhibition at the single-cell level revealed signaling and metabolic changes driven by wild-type Ras at the Golgi and mutant KRas at the mitochondria and that major vault protein mediates these adaptations.
