Aug 2026· Journal of Biological Chemistry· pp.
113510
· 0 citations
Medicine
TL;DR
This study highlights a new role for agmatine in bacterial polyamine biosynthesis, which also includes the N1-aminopropylagmatine and carboxyaminopropylagmatine pathways for spermidine production.
Abstract
Homospermidine is a structural analog of spermidine, a polyamine that is essential for growth and cell proliferation in eukaryotes. The eukaryotic enzyme deoxyhypusine synthase (DHS) can synthesize homospermidine directly from spermidine and putrescine. Nonhomologous bacterial homospermidine synthase (HSS) synthesizes homospermidine directly from two molecules of putrescine. SpeY is a homolog of DHS in bacteria that is essential for homospermidine biosynthesis in a cyanobacterium. Recently, it was shown in the bacterial hyperthermophile Thermus thermophilus, that SpeY couples two molecules of agmatine produced by arginine decarboxylase to form N1,N9-bis(guanidino)homospermidine (G44G), which is then converted to homospermidine by a ureohydrolase. We sought to determine whether synthesis of G44G was a common feature of phylogenetically diverse SpeY homologs. Herein, we demonstrate that SpeY homologs from diverse bacterial phyla, and from species encoding arginine decarboxylases from three different protein folds, with either agmatinase or agmatine iminohydrolase partners, all form G44G. Diverse agmatine, N1-aminopropylagmatine and presumed G44G ureohydrolases convert G44G to homospermidine but SpeY-associated G44G ureohydrolases do not act on agmatine. Similarly, diverse agmatine, N1-aminopropylagmatine and presumed G44G iminohydrolases convert G44G to N1,N9-bis(carbamoyl)homospermidine but SpeY-associated G44G iminohydrolases do not act on agmatine. We identified ornithine decarboxylases in both the SpeY and HSS pathways that have become neofunctionalized to arginine decarboxylases, and in the HSS pathway are associated with an agmatinase. Bacterial homospermidine biosynthetic pathways are therefore dependent either on agmatine/SpeY or putrescine/HSS. Our study highlights a new role for agmatine in bacterial polyamine biosynthesis, which also includes the N1-aminopropylagmatine and carboxyaminopropylagmatine pathways for spermidine production.
This study constructed a pH-responsive P-TN/SF@Fe-Cur composite coating that demonstrated significant anti-infective, anti-inflammatory, antioxidant, pro-angiogenic, and pro-osteogenic effects in rat subcutaneous infection and femoral defect models.
Protein therapeutic design and property prediction are frequently hampered by data scarcity. Here we propose a model, DyAb, that addresses these issues by leveraging a pair-wise representation to predict differences in binding affinity, rather than absolute values. DyAb is built on top of a pre-trained protein language model and achieves a Spearman rank correlation of up to 0.85 on binding affinity prediction across monoclonal antibodies targeting three different antigens (EGFR, IL-6, and an internal target), given as few as 100 training data. We employ DyAb in two design contexts: as a ranking model to score combinations of known mutations, and combined with a genetic algorithm to generate new sequences. Our method consistently generates antibody variants with high binding rates, including designs that improve on the binding affinity of the lead molecule by more than ten-fold. DyAb represents a powerful tool for optimizing antibody binding affinity in low data regimes common in early-stage drug development.
Joshua Yao-Yu Lin, Jennifer L. Hofmann, Andrew Leaver‐Fay et al.· mAbs· 1 citation
Due to its importance and wide adoption, wheat cultivation is promptly required to shift towards sustainable practices, reducing the dependency on chemical components. Among bio-based solutions aimed at securing the sustainability of wheat cultivation, biostimulants offer a versatile platform of eco-friendly tools assuring sustainability and profitability. Microalgae present a concrete example of a biostimulant source due to their richness in metabolites and high value products. Therefore, this study evaluated the biostimulant potential of eleven eco-extracts prepared from soil-isolated microalgae strains. Eco-extracts applied via soil drench at low dose (0.1 g/L) were investigated for their biostimulant effects on wheat growth, physiology, yield, and quality under controlled conditions. Results demonstrated significant ameliorations in treated plants as compared to the control, with no phytoinhibitory effects. Remarkable enhancements were notable in growth parameters such as shoot and root lengths (+40-70%), physiological traits such as total chlorophyll and stomatal conductance (+7-52%), yield components in the example of grain number per spike and thousand grain weight (+17-103%), and grain quality namely protein and polyphenol content (+2-fold to 4-fold). Similarly, phosphorus accumulation and uptake were significantly improved, while soil physicochemical status was ameliorated, indicating enhanced fertility. Multivariate analysis and composite index ranking marked Chlorella sp. GA18, Chlorella sp. GA65, Scenedesmus sp. GA69, and Chlorococcum sp. GA63 as eco-extracts with consistent performances across all plant traits. These findings highlighted the promising potential of integrating microalgae-based eco-friendly extracts in sustainable wheat cultivation.
Amer Chabili, Z. Hakkoum, F. Minaoui et al.· Plant Science· 1 citation
ProteinReasoner is developed, a multimodal generative protein foundation model that sequentially connects amino acid sequence, evolutionary constraints and three-dimensional structure within a shared autoregressive architecture and suggests a general route towards reasoning across interdependent representations in other scientific domains.
Chaozhong Liu, Linlin Chao, Shaomin Ji et al.· bioRxiv· 1 citation
HydroGym is introduced, a solver-independent reinforcement learning platform providing more than 60 validated, openly available flow control environments spanning from canonical laminar flows to complex turbulent flows, with systematic progression in the Reynolds number up to Re = 4 × 105, and Mach number variations in two and three dimensions.
Christian Lagemann, Sajeda Mokbel, Miro Gondrum et al.· Nature· 1 citation
The results show that alternative transcript diversity extensively enters translation-supported proteoform space and establish a systematic link between transcript variation and protein functional diversification.
Felicia T. Jiang, Dengwang Chen, Ziwei Wang et al.· bioRxiv· 1 citation