Open research questions in Polyamine Metabolism and Applications

What the literature leaves open

• AGM decreases the mitochondrial membrane potential and induces mitophagy in IECs remains to be fully elucidated. We hypothesize that the protective effects of AGM against sepsis-induced intestinal injury may not be limited to the direct inhibition of IEC apoptosis.

  Agmatine induces mitophagy via the PTS-I2R pathway to increase autophagic flux and attenuate sepsis-induced intestinal epithelial cell apoptosis · 2026 · DOI

• The enzyme is inhibited at high concentrations of ASA, possibly due to reactions between free amines and the aldehyde functional group. The insertion of an additional helix in the polyamine recognition loop of SpDH does not alter the position of the Asn-Glu-Phe-Glu motif. The need to confirm the residues involved in agmatine specificity through structural analysis.

  Streptococcus pneumoniae Aspartate Semialdehyde-Dependent Dehydrogenase Initiates Polyamine Biosynthesis with Agmatine · 2026 · DOI

• The biosynthesis of spermidine in S. pneumoniae remains incompletely characterized. The role of aspartate semialdehyde dehydrogenase in initiating polyamine biosynthesis is not well understood. The substrate specificity of S. pneumoniae aspartate semialdehyde dehydrogenase is unknown.

  Streptococcus pneumoniae Aspartate Semialdehyde-Dependent Dehydrogenase Initiates Polyamine Biosynthesis with Agmatine · 2026 · DOI

• The differential sensitivity between cancerous and non-malignant prostate cells highlights a novel therapeutic window that warrants further investigation in vivo.

  Targeting Methionine Metabolism Reveals AMPK-SAMTOR Signaling as a Therapeutic Vulnerability in Prostate Cancer · 2025 · DOI

• Despite the significance of spermidine, the role of spermidine in cryoprotection remains to be extensively studied. However, the specific mechanism remains to be elucidated. The precise underlying mechanisms, however, remain to be elucidated. We then proceeded to conduct further research into the effect of spermidine on oxidative stress in frozen oocytes.

  Spermidine Supplementation Effectively Improves the Quality of Mouse Oocytes After Vitrification Freezing · 2025 · DOI

• The current diagnostic biomarkers for histamine intolerance caused by DAO deficiency may not be sufficient. The relationship between serum DAO activity and the genetic load of DAO deficiency-associated gene variants is not well understood. The clinical validity of the measurement of serum DAO activity has been questioned by some authors.

  Pilot Study on the Prevalence of Diamine Oxidase Gene Variants in Patients with Symptoms of Histamine Intolerance · 2024 · DOI

• The development and maturation of the intestine is important for piglets to maintain optimal growth and health. There is a need to understand the role of polyamines in intestinal development and function in piglets.

  The Roles of Polyamines in Intestinal Development and Function in Piglets · 2024 · DOI

• Quality and safety issues in fermented foods need to be addressed. Enzymes can be used to improve the quality and safety of fermented foods. Advanced biological methods are needed to enhance enzymatic activity and stability.

  Recent Applications and Prospects of Enzymes in Quality and Safety Control of Fermented Foods · 2024 · DOI

• Limited understanding of the microbial community of Korean soy sauce. Lack of comprehensive information on the relationship between microbial communities and sensory characteristics.

  Investigation of Microbial Community of Korean Soy Sauce (Ganjang) Using Shotgun Metagenomic Sequencing and Its Relationship with Sensory Characteristics · 2024 · DOI

• Future studies should focus on hurdle technologies where multiple techniques are combined to stop bacteria from adapting to the treatments used, which would in turn increase the feasibility of using them and improve their economic feasibility, particularly in premium and safety-sensetive markets, while also being generally considered safer.

  Advances and challenges in microbial biotechnology for food preservation: a critical review · 2026 · DOI

• Second, the exact synergistic mechanisms between the two strains need to be studied.

  Effects of mixed Lactiplantibacillus plantarum CD101 and Staphylococcus simulans NJ201 on dry fermented sausages · 2026 · DOI

• The formation of biogenic amines during stylo ensiling is not well understood. The effects of formic acid and sugar additives on the fermentation parameters, amino acids profile, biogenic amines formation, and bacterial community of ensiled stylo are not well studied.

  Fermentation Parameters, Amino Acids Profile, Biogenic Amines Formation, and Bacterial Community of Ensiled Stylo Treated with Formic Acid or Sugar · 2024 · DOI

• In this vast superfamily, several types of protein functions have been explored throughout evolution, yet the evolutionary pathways that led to such diversity remain poorly understood.

  Structural plasticity drives convergent evolution and functional diversification of GNAT polyamine acetyltransferases · 2026 · DOI

• There is a need to identify effective natural preservatives to reduce histamine formation in skipjack tuna. The current study aims to address this gap by investigating the inhibitory effects of plant-derived essential oils on the growth and histamine production of Aeromonas hydrophila.

  Plant Essential Oils Inhibit Growth and Histamine Production of Aeromonas hydrophila Isolated from Skipjack Tuna · 2026 · DOI

• Crucially, while constant light-induced degradation is insufficient to rescue growth, oscillating ODC degradation at a 40-minute period restores polyamine homeostasis, cell cycle progression, and cellular growth.

  Optogenetic decoupling of ODC inhibition and degradation reveals a requirement of polyamine oscillation for cell cycle progression · 2026 · DOI

• However, the functional coupling between ODC inhibition and degradation remains poorly understood, and the current therapeutic intervention with DFMO target enzymatic activity without addressing protein accumulation.

  Optogenetic decoupling of ODC inhibition and degradation reveals a requirement of polyamine oscillation for cell cycle progression · 2026 · DOI

• ImportanceBeneficial animal-microbe interactions can shape development, physiology, and behavior in organisms across the tree of life, yet in many cases, the molecular mechanisms driving these interactions remain poorly understood.

  Development and behavior of Steinernema hermaphroditum nematodes are impacted by a bacterial flavin monooxygenase · 2026 · DOI

• The study was an observational retrospective study, - The impact on DAO activity was assumed to be the same for each variant, - The study had a limited sample size of 100 patients and 100 healthy controls, - The clinical validity of the measurement of serum DAO activity has been…

  Pilot Study on the Prevalence of Diamine Oxidase Gene Variants in Patients with Symptoms of Histamine Intolerance · 2024 · DOI

• The complexity of the factors influencing biogenic amine accumulation in cheeses, - The need for a better understanding of the microorganisms and processes that produce or reduce biogenic amines, - The importance of addressing the food security concerns related to biogenic amines…

  A Comprehensive Review on the Biogenic Amines in Cheeses: Their Origin, Chemical Characteristics, Hazard and Reduction Strategies · 2024 · DOI

• Few papers were available in the literature on biogenic amines in goat's milk cheeses, - The presence of biogenic amines in fresh cheeses, kefir, and yoghurt is still unclear, - Cheese ripening is a relative concept and can vary depending on the type of cheese and consumer…

  A Comprehensive Review on the Biogenic Amines in Cheeses: Their Origin, Chemical Characteristics, Hazard and Reduction Strategies · 2024 · DOI

• Investigating the effects of different fermentation times on the microbial community of Korean soy sauce, - Comparing the microbial community of traditional Korean soy sauce to other types of fermented foods, - Selecting starter cultures for soy sauces based on the results…

  Investigation of Microbial Community of Korean Soy Sauce (Ganjang) Using Shotgun Metagenomic Sequencing and Its Relationship with Sensory Characteristics · 2024 · DOI

• Though the precise mechanisms by which hypusination facilitates translation remain to be fully worked out, the consensus is that hypusinated eIF5A…

  Polyamines mediate cellular energetics and lipid metabolism through mitochondrial respiration to facilitate virus replication · 2024 · DOI

• The concentration of antibiotics is unknown, - The concentration of the active compound in the given fractions could not be measured, - There are not many antimicrobial compounds that can directly or indirectly disrupt bacterial transcription and simultaneously have an effect on Gram-negative…

  The Spermidine Synthase Gene as a Reporter of Transcription Inhibition in Escherichia coli · 2026 · DOI

• Screening new potential antibiotics from synthetic molecule libraries and natural sources, - Applying the proposed method in sequential screening procedures to reveal active antimicrobial compounds that inhibit bacterial transcription…

  The Spermidine Synthase Gene as a Reporter of Transcription Inhibition in Escherichia coli · 2026 · DOI

• Investigation of the effectiveness of essential oils under practical storage conditions. Study of the effects of essential oils on other types of bacteria. In vivo experiments to confirm the findings.

  Plant Essential Oils Inhibit Growth and Histamine Production of Aeromonas hydrophila Isolated from Skipjack Tuna · 2026 · DOI

Most-cited papers in Polyamine Metabolism and Applications

• ATP13A2 deficiency disrupts lysosomal polyamine export · Nature · 2020 · 340 citations
• Polyamine metabolism is a central determinant of helper T cell lineage fidelity · Cell · 2021 · 299 citations
• Symbiotic polyamine metabolism regulates epithelial proliferation and macrophage differentiation in the colon · Nature Communications · 2021 · 260 citations
• Amphetamine toxicities · Annals of the New York Academy of Sciences · 2010 · 236 citations
• Polyamines in Mammalian Biology and Medicine · Perspectives in biology and medicine · 1979 · 224 citations
• Human Colon Microbiota Transform Polycyclic Aromatic Hydrocarbons to Estrogenic Metabolites · Environmental Health Perspectives · 2004 · 209 citations
• Polyamines and their possible mechanisms involved in plant physiological processes and elicitation of secondary metabolites · Acta Physiologiae Plantarum · 2018 · 187 citations
• A review of biogenic amines in fermented foods: Occurrence and health effects · Heliyon · 2024 · 169 citations
• Polyamines: Functions, Metabolism, and Role in Human Disease Management · Medical Sciences · 2021 · 149 citations
• Protective Role of Spermidine in Colitis and Colon Carcinogenesis · Gastroenterology · 2021 · 142 citations

Most recent work

• Occurrence and associated factors of biogenic amines in selected Mediterranean dairy products · Journal of Dairy Science · 2026
• Multi-mechanism-driven dual-mode array based on a single PFC-1/QD probe enables AI-assisted on-site identification of biogenic amines and real-time food freshness monitoring · Biosensors and Bioelectronics · 2026
• Recruitment of bifunctional regulator thermospermine to methylated ribosomes directs xylem fate · Science · 2026
• Polyamine metabolism as a regulator of cellular and organismal aging · Amino Acids · 2026
• The role of spermidine in plants and humans: a pathway from climate change adaptation to health benefits · npj Science of Food · 2026
• Statistical insights into biogenic amine accumulation in traditional cheeses based on microbial, physicochemical, proteolytic, and technological properties · Journal of Dairy Science · 2026
• Polyamine pathway in neurological disorders: Potential therapeutic implications based on current evidences · Brain Research Bulletin · 2026
• Parallel evolution of plant alkaloid biosynthesis from bacterial‐like decarboxylases · New Phytologist · 2026
• A comprehensive review on contribution of nanosensors towards detection of tyramine in food: Sensing mechanisms, applications and prospects · Inorganic Chemistry Communications · 2026
• Evaluation of agmatine’s anti-cancer efficacy in Caco-2 colorectal adenocarcinoma cells · Medical Oncology · 2026

Related topics in Biochemistry, Genetics and Molecular Biology