Search Results (175)

Phytochemistry serves as a vital bridge between traditional medicinal knowledge and modern scientific research, with important implications for pharmaceutical and industrial applications. This review offers an updated and integrated perspective on Chelidonium majus (greater celandine), focusing on its isoquinoline alkaloids—the principal bioactive constituents—alongside emerging phytochemicals (e.g., lignanamides, polyphenols). Detailed biosynthetic pathways of isoquinoline alkaloids are described, tracing their formation from the shikimate pathway to multiple structural subclasses. Reported biological activities include anticancer, antioxidant, anti-inflammatory, antimicrobial, antiviral, and immunomodulatory effects. A bibliometric analysis was conducted using VOSviewer software (Scopus dataset, 2015–2025), enabling the identification of major research themes and temporal trends. These research tools supported a structured and data-driven overview of the current scientific landscape. However, additional studies are needed to optimize its therapeutic use while ensuring efficacy and safety. Full article

Antibiotic resistance is considered to be one of the most complex health obstacles of our time. Methicillin-resistant Staphylococcus aureus (MRSA) represents a global health challenge due to its broad treatment resistance capacity, resulting in high mortality rates. The shikimate pathway (SP) is responsible for the biosynthesis of chorismate from glycolysis and pentose phosphate pathway intermediates. This pathway plays a crucial role in producing aromatic amino acids, folates, ubiquinone, and other secondary metabolites in bacteria. Notably, SP is absent in humans, which makes it a specific and potential therapeutic target to explore for discovering new antibiotics against MRSA. The present study characterized in vitro and in silico natural products as inhibitors of the shikimate dehydrogenase from methicillin-resistant S. aureus (SaSDH). The results showed that, from the set of compounds studied, phloridzin, rutin, and caffeic acid were the most potent inhibitors of SaSDH, with IC₅₀ values of 140, 160, and 240 µM, respectively. Furthermore, phloridzin showed a mixed-type inhibition mechanism, whilst rutin and caffeic acid showed non-competitive mechanisms. The structural characterization of the SaSDH–inhibitor complex indicated that these compounds interacted with amino acids from the catalytic site and formed stable complexes. In biological activity studies against MRSA, caffeic acid showed an MIC of 2.2 mg/mL. Taken together, these data encourage using these compounds as a starting point for developing new antibiotics based on natural products against MRSA. Full article

Tryptophan is synthesized in microorganisms via a five-step enzymatic pathway originating from chorismate, which is a product of the shikimate pathway. As a biosynthetic precursor to a wide range of high-value compounds such as indole-3-acetic acid, indigo, indirubin, and violacein, this pathway has been a central target for metabolic engineering to enhance microbial production. Anthranilate phosphoribosyltransferase (AnPRT) catalyzes the second step of the pathway by transferring a phosphoribosyl group from PRPP to anthranilate, forming phosphoribosyl anthranilate (PRA). AnPRT, the sole member of class IV phosphoribosyltransferases, adopts a unique fold and functions as a homodimer. While the structural basis of AnPRT activity has been elucidated in several organisms, thermostable variants remain underexplored despite their relevance for high-temperature bioprocessing. In this study, the crystal structure of AnPRT from the thermophilic archaeon Methanocaldococcus jannaschii (MjAnPRT) was determined at a 2.16 Å resolution. The enzyme exhibits a conserved dimeric architecture and key catalytic motifs. Comparative structural analysis with mesophilic and hyper thermophilic homologs revealed that MjAnPRT possesses enhanced local stability in catalytically important regions and strengthened inter-subunit interactions. These features likely contribute to its thermostability and provide a valuable framework for the rational design of robust AnPRTs for industrial and synthetic biology applications. Full article

The shikimate pathway is the fundamental metabolic route for aromatic amino acid biosynthesis in bacteria, plants, and fungi, but is absent in mammals. This review explores how multi-enzyme synergy and allosteric regulation coordinate metabolic flux through this pathway by focusing on three key enzymes: 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase, chorismate mutase, and tryptophan synthase. We examine the structural diversity and distribution of these enzymes across evolutionary domains, highlighting conserved catalytic mechanisms alongside species-specific regulatory adaptations. The review covers directed evolution strategies that have transformed naturally regulated enzymes into standalone biocatalysts with enhanced activity and expanded substrate scope, enabling synthesis of non-canonical amino acids and complex organic molecules. Industrial applications demonstrate the pathway’s potential for sustainable production of pharmaceuticals, polymer precursors, and specialty chemicals through engineered microbial platforms. Additionally, we discuss the therapeutic potential of inhibitors targeting pathogenic organisms, particularly their mechanisms of action and antimicrobial efficacy. This comprehensive review establishes the shikimate pathway as a paradigmatic system where understanding allosteric networks enables the rational design of biocatalytic platforms, providing blueprints for biotechnological innovation and demonstrating how evolutionary constraints can be overcome through protein engineering to create superior industrial biocatalysts. Full article

The sorghum aphid (Melanaphis sacchari (Zehntner, 1897)), a globally destructive pest, severely compromises sorghum yield and quality. This study compared aphid-resistant (HX133) and aphid-susceptible (HX37) sorghum (Sorghum bicolor (L.) Moench) cultivars, revealing that HX133 significantly suppressed aphid proliferation through repellent and antibiotic effects, while aphid populations increased continuously in HX37. Transcriptome analysis identified 2802 differentially expressed genes (DEGs, 45.9% upregulated) in HX133 at 24 h post-infestation, in contrast with only 732 DEGs (21% upregulated) in HX37. Pathway enrichment highlighted shikimate-mediated phenylpropanoid/flavonoid biosynthesis and glutathione metabolism as central to HX133’s defense response, alongside photosynthesis-related pathways common to both cultivars. qRT-PCR validation confirmed activation of the shikimate pathway in HX133, driving the synthesis of dhurrin—a cyanogenic glycoside critical for aphid resistance—and other tyrosine-derived metabolites (e.g., benzyl isoquinoline alkaloids, tocopherol). These findings demonstrate that HX133 employs multi-layered metabolic regulation, particularly dhurrin accumulation, to counteract aphid infestation, whereas susceptible cultivars exhibit limited defense induction. This work provides molecular targets for enhancing aphid resistance in sorghum breeding programs. Full article

2-Phenylethanol (2-PE), an aromatic alcohol with a rose-like fragrance, is widely used in the food, pharmaceutical, and high-end cosmetic industries. In this study, a high-yield 2-PE-producing strain was isolated and identified as Saccharomyces cerevisiae based on morphological characterization and taxonomic identification. Fermentation medium components (carbon and nitrogen sources) were optimized through single-factor experiments in shaking flasks, and fermentation medium with 40 g/L glucose, 5 g/L malt extract, 1.75 g/L corn steep liquor, 2.5 g/L yeast extract, 5 g/L malt extract, 1.75 g/L corn steep liquor was considered suitable for 2-PE production. RT-qPCR results indicated that corn steep liquor activates expression of genes related to the shikimate pathway and Ehrlich pathway (pha2, aro4, aro8, and aro9), thereby promoting the synthesis of 2-PE through these pathways. Excess yeast extract inhibited the expression of aro8 and aro9, while enhancing the expression of tdh3 and adh2, thus promoting the de novo synthesis of 2-PE. Furthermore, fermentation in a 5 L bioreactor was applied to investigate the effects of feeding strategies, inoculum proportion, and pH on 2-PE production. With a pH of 5.5 and10% inoculum proportion, the supplementation of the substrate L-Phe led to a 2-PE production of 4.81 g/L after 24 h of fermentation. Finally, in situ product recovery (ISPR) techniques was applied to alleviate 2-PE cytotoxicity, achieving a production of 6.41 g/L. This process offers a promising strategy for producing 2-PE efficiently and naturally, paving the way for further industrial applications in food, pharmaceutical, and cosmetic sectors. Full article

Nano-titanium dioxide (nano-TiO₂) can alleviate oxidative damage in plants subjected to abiotic stress, interfere with related gene expression, and change metabolite content. Polylactic acid (PLA) microplastics can inhibit plant growth, induce oxidative stress in plant cells, and alter the biophysical properties of rhizosphere soil. In this study, untargeted metabolomics (LC-MS) and RNA-seq sequencing were performed on radish root cells exposed to nano-TiO₂ and PLA. The results showed that nano-TiO₂ alleviated the growth inhibition of radish roots induced by PLA. Nano-TiO₂ alleviated PLA-induced oxidative stress, and the activities of SOD and POD were decreased by 28.6% and 36.0%, respectively. A total of 1673 differentially expressed genes (DEGs, 844 upregulated genes, and 829 downregulated genes) were detected by transcriptome analysis. Metabolomics analysis showed that 5041 differential metabolites were involved; they mainly include terpenoids, fatty acids, alkaloids, shikimic acid, and phenylpropionic acid. Among them, phenylpropanoid biosynthesis as well as flavone and flavonol biosynthesis were the key metabolic pathways. This study demonstrates that nano-TiO₂ mitigates PLA phytotoxicity in radish via transcriptional and metabolic reprogramming of phenylpropanoid biosynthesis. These findings provide important references for enhancing crop resilience against pollutants and underscore the need for ecological risk assessment of co-existing novel pollutants in agriculture. Full article

Apricot is one of the most important Mediterranean fruits with high diversity and fruit quality properties, being an excellent raw material for polyphenol compounds. This study aimed to determine the anthocyanin, quercetin glycoside and phenolic acid contents in new apricot genotypes from the breeding program at the Instituto Valenciano de Investigaciones Agrarias, confirming the potential of the ‘Goldrich’ cultivar to be a parental donor for increasing the antioxidant content, which would, in turn, enhance fruit quality. Phenolic composition of the apricot accessions is strongly genotype-dependent, with the concentrations of overall total phenolic compounds ranging from 770 to 260 mg 100 g⁻¹ DW, reflecting significant genetic diversity. ‘Goldrich’ contributed to the polyphenol content; however, its influence varied across derived varieties, with ‘GG9310’ and ‘GG979’ enhancing the shikimic acid pathway and accumulating high levels of total phenolics. In contrast, ‘Mitger’ and ‘HG9850’ stood out for high anthocyanin synthesis, despite their lower levels of flavonols and phenolic acids. The predominant anthocyanin was cyanidin-3-O-rutinoside, followed by cyanidin-3-O-glucoside and peonidin-3-O-rutinoside in smaller amounts. Other phenolics were rutin and quercetin-3-O-glucuronide, as well as neochlorogenic and chlorogenic acids. The PCA model was applied to all data to identify the most attractive cultivars, and chromatographic analysis was performed in a short time using Ultra-High-Performance Liquid Chromatography (UHPLC) with diode array and mass spectrometric detection. Apricot peel is an excellent source of nutraceutical compounds with a chemical composition strongly determined by the cultivar. Results can help establish authenticity markers for apricot cultivars. Full article

Chilling injury can limit the productivity of tomato (Solanum lycopersicum L.), especially in over-wintering greenhouse. We here explored the effect of the pre-application of chlorogenic acid (CGA) in mitigating the impact of chilling on tomato. Flowering plants subjected to either chilling (15 °C/5 °C, day/night) or pre-treatment with CGA followed by chilling for 6 days and then by a two-day control recovery period were compared to plants maintained at control conditions (25 °C/18 °C, day/night). Chilling significantly affected the expression of PSII CP43 Chlorophyll Apoprotein, NAD (P) H-Quinone Oxidoreductase Subunit 5 and ATP Synthase CF1 Beta Subunit, reduced leaf Fv/Fm and increased malondialdehyde (MDA) levels, suggesting elevated oxidative stress. These correlated with reduced shoot biomass. All these aspects were mitigated by pretreatment with CGA. Transcriptomic and metabolomic co-analysis indicated that CGA also suppressed the shikimate pathway, phenylpropanoid biosynthesis and phenylalanine accumulation but enhanced cinnamic acid and indole acetate synthesis. Hence, the pre-chilling CGA protected the tomato plant from chilling injury by maintaining light energy utilization and reprograming secondary metabolism. This study describes the mechanism through which CGA pre-treatment can be used to maintain tomato productivity under chilling conditions. Full article

Phenolic compounds (PCs) are key secondary metabolites in horticultural plants that are structurally categorized into flavonoids, simple phenols, stilbenes, and tannins. Synthesized via the shikimate and phenylpropanoid pathways, the metabolism of PCs is regulated by transcription factors (e.g., MYB and bZIP) and influenced by genetic backgrounds and environmental stresses (e.g., temperature and UV), thereby leading to species- or tissue-specific distribution patterns. Advanced extraction/separation techniques (e.g., ultrasonic-assisted and HPLC) have enabled systematic PC characterization. Functionally, PCs enhance plant stress resistance (abiotic/biotic) through antioxidant activity, cell wall reinforcement, and defense signaling. Their dual roles as reactive oxygen species scavengers, and signaling molecules are integral. This review synthesizes the classification, metabolic regulation, and biological functions of PCs, providing a scientific basis for improving PC content in horticultural plants with the aim of enhancing stress resilience, postharvest and storage quality, and nutritional value for sustainable agriculture. Full article

Mandelic acid (MA) is a valuable α-hydroxy acid with applications in pharmaceuticals, cosmetics, and fine chemicals. While chemical synthesis is well established, concerns over toxicity and sustainability have driven interest in microbial production. Here, we engineered Escherichia coli for de novo MA biosynthesis by integrating enzyme screening, metabolic flux optimization, and pathway regulation. We first screened and identified an efficient hydroxymandelate synthase (HMAS) homolog from Actinosynnema mirum for MA synthesis, and subsequently enhanced the shikimate pathway along with the supply of the precursors erythrose-4-phosphate (E4P) and phosphoenolpyruvate (PEP). Additionally, CRISPR interference (CRISPRi) was employed to repress competing pathways and redirect flux toward MA production. High-cell-density cultivation (HCDC) in a 5 L bioreactor demonstrated the strain’s industrial potential, achieving an MA titer of 9.58 g/L, the highest reported for microbial production. This study provides a systematic metabolic engineering approach for efficient MA biosynthesis from glucose, offering a foundation for sustainable large-scale production, demonstrating not only genetic-level optimizations, but also effective process scaling through high-cell-density cultivation, highlighting the power of pathway engineering in microbial cell factories. Full article

Glyphosate (N-phosphonomethylglycine) is a widely used organophosphorus herbicide that inhibits the shikimate pathway, a crucial metabolic route responsible for the synthesis of aromatic amino acids in plants and certain microorganisms. Due to its broad-spectrum activity, glyphosate serves as the main active ingredient in various commercial herbicide formulations, including Roundup and Kalach 360 SL (KL). It poses a health hazard to animals and humans due to its persistence in soil, water erosion, and crops. The aim of our study was to continue the previous research to explore the impact of KL on bone using physico-chemical parameters and in silico studies after exposing female wistar rats for 60 days. The in silico study concerned the assessment of binding affinity and molecular interactions using computational modeling approach. The rats were allocated into three experimental groups: group 1 (n = 6) served as controls, while groups 2 and 3 received low and high doses (Dose 1: 126 mg/Kg and Dose 2: 315 mg/Kg) of KL dissolved in water, respectively. All rats were sacrificed after 60 days of exposure. XRD and FTIR spectrum analysis of bone tissues in female rats showed significant histoarchitectural changes associated with bone mineralization disruption. Our results have demonstrated that sub-chronic exposure of adult female rats to KL causes bone rarefaction, as confirmed by a previous histological study. This physico-chemical study has further confirmed the harmful impact of KL on the crystalline fraction of bone tissue, composed of hydroxyapatite crystals. In addition, the computational analyses showed that glyphosate binds to 3 Glu form of osteocalcin (3 Glu-OCN) (4MZZ) and decarboxylated osteocalcin (8I75) with good affinities and strong molecular interactions, which justified and supported the in vivo findings. In conclusion, KL may interfere with hydroxyapatite and osteocalcin and, therefore, impair bone remodeling and metabolism. Full article

Water used in cleaning processes within the agri-food industry can be a vector for post-harvest contaminants, thus contributing to cross-contamination. The contamination risk is increased when water is not replaced between batches or when disinfection protocols are insufficient. Given the increasing focus in recent years on the potential of natural, non-invasive plant extracts to combat a variety of pathogens, including multidrug-resistant bacteria, environmental strains, and clinical isolates, this study aimed to evaluate the antibacterial activity of selected water-ethanol plant extracts against six opportunistic pathogens isolated from wash water in the agri-food industry, along with chromatographic analyses of the selected extracts. Plant extracts were obtained from the fruits, leaves, shoots, roots, and bark of 13 species. Antibacterial activity was assessed using the well diffusion method. The results indicated that antimicrobial activity was exhibited by six extracts: Tilia cordata Mill., Camellia sinensis, Quercus robur L., Betula pendula Roth, Rubus idaeus L., and Salix alba L. The extracts showed strain-dependent antimicrobial activity, with C. sinensis and R. idaeus up to 4.0 mm and 8.0 mm inhibition zones, respectively. P. aeruginosa and E. faecalis were the most susceptible strains, demonstrating the largest inhibition zones. In contrast, P. vulgaris and K. oxytoca were more resistant. The efficacy of the most active extracts can be linked to the presence of phytochemicals identified via GC-MS, including epicatechin, shikimic acid, quinic acid, gallic acid, and caffeine. These metabolites are known to interfere with bacterial cell structures and metabolic pathways. These studies may serve as a preliminary step toward the development of non-invasive water treatment methods for wash water. Full article

Background/Objectives: In recent years, interest in studying changes in cancer metabolites has resulted in significant advances in the metabolomics field. Glioblastoma remains the most aggressive and lethal brain malignancy, which presents with notable metabolic reprogramming. Methods: We performed literature research from the PubMed database and considered research articles focused on the key metabolic pathways altered in glioblastoma (e.g., glycolysis, lipid metabolism, TCA cycle), the role of oncometabolites and metabolic plasticity, and the differential expression of metabolites in glioblastoma. Currently used metabolomics approaches can be either targeted, focusing on specific metabolites and pathways, or untargeted, which involves data-driven exploration of the metabolome and also results in the identification of new metabolites. Data processing and analysis is of great importance and can be improved with the integration of machine learning approaches for metabolite identification. Results: Changes in α/β-glucose, lactate, choline, and 2-hydroxyglutarate were detected in glioblastoma compared with non-tumor tissues. Different metabolites such as fumarate, tyrosine, and leucine, as well as citric acid, isocitric acid, shikimate, and GABA were detected in blood and CSF, respectively. Conclusions: Although promising new technological and bioinformatic approaches help us understand glioblastoma better, challenges associated with biomarker availability, tumor heterogeneity, interpatient variability, standardization, and reproducibility still remain. Metabolomics research, either alone or combined with genomics or proteomics (i.e., multiomics) in glioblastoma, can lead to biomarker identification, tracking of metabolic therapy response, discovery of novel metabolites and pathways, and identification of potential therapeutic targets. Full article

Methylparaben (MP) is an important member of the paraben family of aromatic compounds, which is under great demand in the industrial market as an antibacterial agent, preservative, and feed additive, and also has potential application value in the preparation of bio-based polyetherester materials. However, the current chemical production method of MP has various problems, such as serious environmental pollution, its dependence on petrochemical resources, and the generation of different types of waste. It is of great significance to develop an environmentally friendly MP synthesis method via synthetic biology. In this work, Saccharomyces cerevisiae was used as the host to construct the biosynthetic pathway of MP and various metabolic engineering strategies were applied to break the bottlenecks in the synthesis process, including the regulation of the rate-limiting steps in the endogenous shikimate pathway, the enhancement of central carbon flux via knocking out competitive pathways and promoting precursors synthesis, and the improvement of the exogenous enzyme expression using promoter engineering. The final engineered S. cerevisiae could produce 68.59 mg/L MP in shake flasks, which was the highest titer of MP synthesized by S. cerevisiae so far. It was indicated that the strategies applied in our work were effective in promoting the synthesis of MP, which not only laid an important foundation for the industrial production of MP, but also provided a platform for the synthesis of other aromatic compounds. Full article