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Chen, Chen et al. report on synergistic yeast consortia using auxotrophic yeast strains to mimic the collaborative interactions in plant multicellular systems, enabling the de novo biosynthesis of complex natural product lignans. The cover image depicts the synergistic yeast consortia.
Lignans are valuable plant natural products with complex structures hampering their production by chemical synthesis and metabolic engineering. Splitting their biosynthetic pathway in a yeast consortium avoids intermediate hijacking and restores an efficient biosynthetic flux, suggesting a method for their future biotechnological supply.
The discovery of seven soybean genes completes the biosynthetic pathway to major glyceollins, granting access to heterologous production and exploration of their antimicrobial potential.
The mechanistic basis for spreading ferroptosis to neighboring cells remains unclear. Galectin-13, a secreted galectin, is now identified as a pivotal mediator of ferroptosis propagation and a determinant of cancer cell ferroptosis sensitivity.
Peroxisomes have emerged as ideal compartments for hosting heterologous biochemical reactions. A study establishes a modular chauffeur strategy for functional expression and trafficking of multi-spanning transporters and integral membrane enzymes into the yeast peroxisomal membrane for metabolic engineering.
The discovery of lipoamide offers a unique approach to modulate stress granule dynamics. It will advance studies of stress granule biology and inform the therapeutic modification of these biomolecular condensates as a potential treatment option for amyotrophic lateral sclerosis.
We present a versatile, chemo-ribosomal approach to generating isolable quantities of protein-derived biopolymers containing site-specific backbone modifications, including β-, γ- and δ-peptide linkages. Two of these extended backbones would be difficult to establish by alternative strategies in folded, full-length proteins generated in cells.
We uncovered the function of a cell-bound biosurfactant, a glycine-glucolipid from Alcanivorax borkumensis that is synthesized via an unusual non-ribosomal peptide synthetase pathway. The glycine-glucolipid enhances microbial adhesion to oil droplets, enabling rapid degradation of the oil. Our research provides insights into advanced bioremediation strategies.
Reconstructing the biosynthesis of complex natural products in yeast is challenging. Here the authors construct a yeast consortium with obligate mutualism aiming to alleviate metabolic promiscuity through the multicellular division of labor, similar to plants, for de novo synthesis of complex antiviral lignans.
Biosynthesis of antimicrobial phytoalexin glyceollins in soybean is complicated and elusive. Here Xie et al. report a plant chassis for high-yield isoflavonoid production, leading to the identification of six P450s that complete the 15-step biosynthesis of diverse glyceollins, which are critical compounds for plant defense.
Grayson et al. report the genomic discovery and biochemical characterization of a widely distributed gene cluster family for briarane diterpenoid biosynthesis in metazoans. This study expands our understanding of the metazoan specialized metabolism, revealing the use of biosynthetic gene clusters by octocorals.
A nanobody was identified that targets the N-terminal fragment of the adhesion G-protein-coupled receptor ADGRG2, allosterically enhances activation by the natural agonist dehydroepiandrosterone and restores signaling in mutant receptors.
Cells undergoing ferroptosis secrete Galectin-13, which binds to CD44 and inhibits the plasma membrane localization of SLC7A11 in neighboring cells, thereby accelerating neighboring cell death and promoting ferroptosis propagation.
A modular protein engineering strategy was developed to shuttle transporters and integral membrane enzymes folded in the endoplasmic reticulum to the peroxisomal membrane. This approach expands the repertoire of biosynthetic pathways that can be compartmentalized in the peroxisome.
Evaluating the off-target effect is crucial for ensuring the safety of CRISPRâCas9-based technologies. Duan, Gao and Zhang et al. developed TOPO-seq, a method to capture and evaluate DNA topology-regulated off-target activity of Cas9-based genome-editing tools.
Wei et al. found that the nuclear E3 ligase ubiquitin protein ligase E3 component n-recognin 5 (UBR5) ubiquitinated VGLL4 at Lys61 for its degradation, which permits HippoâYAP signaling for the development of liver biliary system in mice and multiple cancers in humans.
Uechi et al. found that a small-molecule lipoamide dissolves stress granules (SGs) by targeting SFPQ, a redox-sensitive disordered SG protein, alleviating pathological phenotypes caused by amyotrophic lateral sclerosis-associated FUS and TDP-43 mutants.
Amari et al. developed a condensate-based approach, named ControLD, for reversible trapping and release of lipid droplets inside living cells, temporarily halting their functions, enabling detailed study of lipid droplet biology and their interactions with other cellular structures.
Temporal oscillations in the abundance of different phospholipid species during the yeast cell cycle are reported, suggesting regulation and interplay of phospholipid synthesis, membrane fluidity and metabolic efficiency during cell division.
Palmitoylation at C64 in stimulator of interferon genes (STING) is reported and, along with engagement of C91, is involved in dynamic cross talk with C148 to alter STING oligomer states and ultimately control STING activation.
A post-translational backbone extension acyl rearrangement (BEAR) reaction has now been developed that converts a ribosomal protein product into a new product containing a β-peptide, γ-peptide or δ-peptide backbone. BEAR reactions represent a general strategy to install extended backbones into genetically encoded proteins and peptides expressed in cells.
Alcanivorax borkumensis is a marine, oil-degrading bacterium. Here, the authors describe the synthesis of a cellular biosurfactant. Loss of the biosurfactant affects attachment of mutant cells to the oilâwater interface, highlighting its importance for biofilm formation on oil droplets.