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[学术文献 ] Genome synthesis in plants 进入全文
Nature Reviews Bioengineering
Owing to advances in genome sequencing and editing, a genome can now be redesigned, synthesized and introduced into cells as desired. The field of synthetic genomics not only aims to provide deeper understanding of how the genome functions but can also be harnessed for a wide range of synthetic biology and bioengineering applications, from rapid evolution and screening for favourable strains to biotechnological and bioproduction tool development. Although genome synthesis has been carried out mainly in simple unicellular organisms, plants and animals are now also being investigated. Compared with animals, plants have unique advantages, such as fewer ethical concerns, simpler experimental operations and easier regeneration from cells to organisms. In this Review, we focus on genome synthesis in plants, discuss the current research landscape and assess possible future directions.
[前沿资讯 ] DeepMind’s latest AI tool makes sense of changes in the human genome 进入全文
Science
AlphaGenome, is expected to make it easier for researchers to pinpoint the causes of diseases by more accurately tracking the consequences of genetic mutations, and help synthetic biologists design new genes from scratch. DeepMind officials say they are still working out how they will make the tool commercially available. But academic researchers can use it for free.AlphaGenome unites many of these analyses and others into a single package. It relies on massive molecular biology databases produced over decades by publicly funded consortia. These include the results of experiments tracking how certain mutations in human and mouse cells affect properties such as the production of RNA, which translates the genome’s blueprints into proteins, and levels of transcription factors, proteins that can turn genes on and off. By training on those data sets, AlphaGenome has learned to decipher DNA, identifying both genes and the nongene sequences that orchestrate gene activity, along with the genetic variants most likely to produce consequential changes.
[学术文献 ] Cell state-specific cytoplasmic density controls spindle architecture and scaling 进入全文
Nature Cell Biology
Mitotic spindles are dynamically intertwined with the cytoplasm they assemble in. How the physicochemical properties of the cytoplasm affect spindle architecture and size remains largely unknown. Using quantitative biochemistry in combination with adaptive feedback microscopy, we investigated mitotic cell and spindle morphology during neural differentiation of embryonic stem cells. While tubulin biochemistry and microtubule dynamics remained unchanged, spindles changed their scaling behaviour; in differentiating cells, spindles were considerably smaller than those in equally sized undifferentiated stem cells. Integrating quantitative phase imaging, biophysical perturbations and theory, we found that as cells differentiated, their cytoplasm became more dilute. The concomitant decrease in free tubulin activated CPAP (centrosomal P4.1-associated protein) to enhance the centrosomal nucleation capacity. As a consequence, in differentiating cells, microtubule mass shifted towards spindle poles at the expense of the spindle bulk, explaining the differentiation-associated switch in spindle architecture. This study shows that cell state-specific cytoplasmic density tunes mitotic spindle architecture. Thus, we reveal physical properties of the cytoplasm as a major determinant in organelle size control.
[学术文献 ] Chromosome-level genome assembly of cultivated strawberry ‘Seolhyang’ (Fragaria × ananassa) 进入全文
Scientific Data
Cultivated strawberry (Fragaria × ananassa) belongs to the family Rosaceae and is an allo-octoploid species (2n = 8× = 56). Using PacBio Revio long reads of ‘Seolhyang’, we completed telomere-to-telomere phased genome assemblies with a size of 797 Mb with a contig N50 of 27.04 Mb. Benchmarking of the universal single-copy orthologs (BUSCO) analysis detected 99.1% conserved genes in the assembly. In addition, the average long terminal repeat assembly index (LAI) was 17.28, with high genome continuity. In this study, we identified 50 of the possible 56 telomeres across 28 chromosomes. The ‘Seolhyang’ genome was annotated using RNA-Seq data representing various F. × ananassa tissues from the NCBI sequence read archive, which resulted in 129,184 genes.
[学术文献 ] Sucrose-driven carbon redox rebalancing eliminates the Crabtree effect and boosts energy metabolism in yeast 进入全文
Nature Communications
Saccharomyces cerevisiae primarily generates energy through glycolysis and respiration. However, the manifestation of the Crabtree effect results in substantial carbon loss and energy inefficiency, which significantly diminishes product yield and escalates substrate costs in microbial cell factories. To address this challenge, we introduce the sucrose phosphorolysis pathway and delete the phosphoglucose isomerase gene PGI1, effectively decoupling glycolysis from respiration and facilitating the metabolic transition of yeast to a Crabtree-negative state. Additionally, a synthetic energy system is engineered to regulate the NADH/NAD ratio, ensuring sufficient ATP supply and maintaining redox balance for optimal growth. The reprogrammed yeast strain exhibits significantly higher yields of various non-ethanol compounds, with lactic acid and 3-hydroxypropionic acid production increasing by 8- to 11-fold comparing to the conventional Crabtree-positive strain. This study describes an approach for overcoming the Crabtree effect in yeast, substantially improving energy metabolism, carbon recovery, and product yields.
[学术文献 ] Ipecac alkaloid biosynthesis in two evolutionarily distant plants 进入全文
Nature Chemical Biology
Ipecac alkaloids are medicinal monoterpenoid-derived tetrahydroisoquinoline alkaloids found in two distantly related plants: Carapichea ipecacuanha (Gentianales) and Alangium salviifolium (Cornales). Here we provide evidence suggesting that both plants initiate ipecac alkaloid biosynthesis through a nonenzymatic Pictet–Spengler reaction and we elucidate the biosynthetic fate of both the 1R and 1S stereoisomers that are produced in this nonstereoselective reaction. Although the biosynthesis of the 1S-derived protoemetine proceeds according to the same chemical logic in both species, each plant uses a distinct monoterpene precursor. Phylogenetic analyses show examples of independent pathway evolution through parallel and convergently evolved enzymes. This work provides insight into how nature can capitalize on highly reactive starting substrates and the manner in which multistep pathways can arise and lays the foundation for metabolic engineering of these important medicinal compounds.
