- Long-term prognosis of 35 patients with methionine adenosyltransferase deficiency based on newborn screening in China. [Journal Article]
- Methionine adenosyltransferase deficiency (MATD) is a rare metabolic disorder caused by mono- or biallelic MAT1A mutations that are not yet well understood. Of the 4,065,644 neonates screened between November 2010 and December 2021, 35 individuals have been diagnosed with an estimated incidence of 1: 116,161 by a cutoff value of methionine 82.7 μmol/L and follow-up over 11 years. MATD patients wi…
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- A decrease in NR2B expression mediated by DNA hypermethylation induces perioperative neurocognitive disorder in aged mice. [Journal Article]CNS Neurosci Ther. 2023 Jan 24 [Online ahead of print]CN
- CONCLUSIONS: Laparotomy cause hippocampus-dependent cognitive decline by hypermethylating the NR2B gene, allowing us to understand the pathogenesis of PND in an epigenetic landscape.
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- Discovery of a Novel Covalent EZH2 Inhibitor Based on Tazemetostat Scaffold for the Treatment of Ovarian Cancer. [Journal Article]J Med Chem. 2023 Jan 24 [Online ahead of print]JM
- Enhancer of zeste homologue 2 (EZH2) is the enzymatic catalytic subunit of polycomb repressive complex 2 (PRC2), which plays an important role in post-translational modifications of histones. In this study, we designed and synthesized a new series EZH2 covalent inhibitors that have rarely been reported. Biochemical studies and mass spectrometry provide information that SKLB-03220 could covalently…
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- Screening for small molecule inhibitors of SAH nucleosidase using an SAH riboswitch. [Journal Article]Anal Biochem. 2023 Jan 19 [Online ahead of print]AB
- Due to the emergence of multidrug resistant pathogens, it is imperative to identify new targets for antibiotic drug discovery. The S-adenosylhomocysteine (SAH) nucleosidase enzyme is a promising target for antimicrobial drug development due to its critical functions in multiple bacterial processes including recycling of toxic byproducts of S-adenosylmethionine (SAM)-mediated reactions and produci…
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- Effects of Poty-Potexvirus Synergism on Growth, Photosynthesis and Metabolite Status of Nicotiana benthamiana. [Journal Article]
- Mixed virus infections threaten crop production because interactions between the host and the pathogen mix may lead to viral synergism. While individual infections by potato virus A (PVA), a potyvirus, and potato virus X (PVX), a potexvirus, can be mild, co-infection leads to synergistic enhancement of PVX and severe symptoms. We combined image-based phenotyping with metabolite analysis of single…
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- Revisiting One-Carbon Metabolites in Human Breast Milk: Focus on S-Adenosylmethionine. [Journal Article]
- Breastfeeding is the gold standard for early nutrition. Metabolites from the one-carbon metabolism pool are crucial for infant development. The aim of this study is to compare the breast-milk one-carbon metabolic profile to other biofluids where these metabolites are present, including cord and adult blood plasma as well as cerebrospinal fluid. Breast milk (n = 142), cord blood plasma (n = 23), m…
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- 3-(Adenosylthio)benzoic Acid Derivatives as SARS-CoV-2 Nsp14 Methyltransferase Inhibitors. [Journal Article]
- SARS-CoV-2 nsp14 guanine-N7-methyltransferase plays an important role in the viral RNA translation process by catalyzing the transfer of a methyl group from S-adenosyl-methionine (SAM) to viral mRNA cap. We report a structure-guided design and synthesis of 3-(adenosylthio)benzoic acid derivatives as nsp14 methyltransferase inhibitors resulting in compound 5p with subnanomolar inhibitory activity …
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- Mining an O-methyltransferase for de novo biosynthesis of physcion in Aspergillus nidulans. [Journal Article]Appl Microbiol Biotechnol. 2023 Jan 17 [Online ahead of print]AM
- Physcion is one of natural anthraquinones, registered as a novel plant-derived fungicide due to its excellent prevention of plant disease. However, the current production of physcion via plant extraction limits its yield promotion and application. Here, a pair of polyketide synthases (PKS) in emodin biosynthesis were used as probes to mining the potential O-methyltransferase (OMT) responsible for…
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- Novel strategies to reverse chemoresistance in colorectal cancer. [Review]Cancer Med. 2023 Jan 16 [Online ahead of print]CM
- Colorectal cancer (CRC) is a common gastrointestinal malignancy with high morbidity and fatality. Chemotherapy, as traditional therapy for CRC, has exerted well antitumor effect and greatly improved the survival of CRC patients. Nevertheless, chemoresistance is one of the major problems during chemotherapy for CRC and significantly limits the efficacy of the treatment and influences the prognosis…
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- S-adenosylmethionine blocks tumorigenesis and with immune checkpoint inhibitor enhances anti-cancer efficacy against BRAF mutant and wildtype melanomas. [Journal Article]
- Despite marked success in treatment with immune checkpoint inhibitor (CPI), only a third of patients are responsive. Thus, melanoma still has one of the highest prevalence and mortality rates; which has led to a search for novel combination therapies that might complement CPI. Aberrant methylomes are one of the mechanisms of resistance to CPI therapy. S-adenosylmethionine (SAM), methyl donor of i…
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- S-adenosylmethionine improves cognitive impairment in D-galactose-induced brain aging by inhibiting oxidative stress and neuroinflammation. [Journal Article]J Chem Neuroanat. 2023 Jan 08; 128:102232.JC
- Oxidative stress and neuroinflammation play crucial roles in aging. S-adenosylmethionine (SAM), a popular supplement, is a potential antioxidant and candidate therapy for depression. This study aimed to evaluate the neuroprotective effects of SAM on D-galactose-induced brain aging and explore its underlying mechanisms. Brain aging model was established with D-galactose (180 mg/kg/day) for 8 weeks…
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- Vitamin D, Folic Acid and Vitamin B12 Can Reverse Vitamin D Deficiency-Induced Learning and Memory Impairment by Altering 27-Hydroxycholesterol and S-Adenosylmethionine. [Journal Article]
- The cholesterol-oxidized metabolite 27-hydroxycholesterol (27-OHC) is synthesized by CYP27A1, which is a key factor in vitamin D and oxysterol metabolism. Both vitamin D and 27-OHC are considered to play important roles in Alzheimer's disease (AD). The study aims to research the effects of co-supplementation of vitamin D, folic acid, and vitamin B12 on learning and memory ability in vitamin D-def…
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- Functional Diversification and Structural Origins of Plant Natural Product Methyltransferases. [Review]
- In plants, methylation is a common step in specialized metabolic pathways, leading to a vast diversity of natural products. The methylation of these small molecules is catalyzed by S-adenosyl-l-methionine (SAM)-dependent methyltransferases, which are categorized based on the methyl-accepting atom (O, N, C, S, or Se). These methyltransferases are responsible for the transformation of metabolites i…
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- Anammox Bacterial S-Adenosyl-l-Methionine Dependent Methyltransferase Crystal Structure and Its Interaction with Acyl Carrier Proteins. [Journal Article]
- Ladderane lipids (found in the membranes of anaerobic ammonium-oxidizing [anammox] bacteria) have unique ladder-like hydrophobic groups, and their highly strained exotic structure has attracted the attention of scientists. Although enzymes encoded in type II fatty acid biosynthesis (FASII) gene clusters in anammox bacteria, such as S-adenosyl-l-methionine (SAM)-dependent enzymes, have been propos…
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- Co-Targeting Luminal B Breast Cancer with S-Adenosylmethionine and Immune Checkpoint Inhibitor Reduces Primary Tumor Growth and Progression, and Metastasis to Lungs and Bone. [Journal Article]
- Breast cancer (BCa) is the most prevalent cancer in females and has a high rate of mortality, especially due to increased metastasis to skeletal and non-skeletal sites. Despite the marked clinical accomplishment of immune checkpoint inhibitor (CPI) therapy in patients with several cancers, it has had limited success in luminal subtypes of BCa. Accordingly, recent efforts have focused on combinati…
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- Engineered geranyl diphosphate methyltransferase produces 2-methyl-dimethylallyl diphosphate as a noncanonical C6 unit for terpenoid biosynthesis. [Journal Article]
- Terpenoids constitute the largest class of natural products with complex structures, essential functions, and versatile applications. Creation of new building blocks beyond the conventional five-carbon (C5) units, dimethylallyl diphosphate (DMAPP) and isopentenyl diphosphate, expands significantly the chemical space of terpenoids. Structure-guided engineering of an S-adenosylmethionine-dependent …
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- Structures and mechanisms of tRNA methylation by METTL1-WDR4. [Journal Article]Nature. 2023 Jan; 613(7943):383-390.Nat
- Specific, regulated modification of RNAs is important for proper gene expression1,2. tRNAs are rich with various chemical modifications that affect their stability and function3,4. 7-Methylguanosine (m7G) at tRNA position 46 is a conserved modification that modulates steady-state tRNA levels to affect cell growth5,6. The METTL1-WDR4 complex generates m7G46 in humans, and dysregulation of METTL1-W…
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- Abnormal methylation caused by folic acid deficiency in neural tube defects. [Review]
- Neural tube closure disorders, including anencephaly, spina bifida, and encephalocele, cause neural tube defects (NTDs). This congenital disability remained not only a major contributor to the prevalence of stillbirths and neonatal deaths but also a significant cause of lifelong physical disability in surviving infants. NTDs are complex diseases caused by multiple etiologies, levels, and mechanis…
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- Case Report: Adenosine kinase deficiency diagnosed 10 years after liver transplantation: Novel phenotypic insights. [Case Reports]
- Adenosine kinase (ADK) deficiency is a rare inborn error of methionine and adenosine metabolism. So far, a total of 27 patients with ADK deficiency have been reported. Here, we describe the first Polish patient diagnosed with ADK deficiency, aiming to highlight the clinical presentation of disease, emphasize diagnostic difficulties, and report the long-term follow-up. Six-month-old patient presen…
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- Improving ATP availability by sod1 deletion with a strategy of precursor feeding enhanced S-adenosyl-L-methionine accumulation in Saccharomyces cerevisiae. [Journal Article]Enzyme Microb Technol. 2023 Mar; 164:110189.EM
- S-adenosyl-L-methionine (SAM), used in diverse pharmaceutical applications, was biosynthesized from L-methionine (L-met) and adenosine triphosphate (ATP). This study aims to increase the accumulation of SAM in Saccharomyces cerevisiae by promoting ATP availability. Strain ΔSOD1 was obtained from the parent strain WT15-33 (CCTCC M 2021915) by deleting gene sod1, which improved the supply of ATP. T…
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- Metabolic engineering of Escherichia coli for the production of (R)-α-lipoic acid. [Journal Article]Biotechnol Lett. 2023 Feb; 45(2):273-286.BL
- CONCLUSIONS: The method described here can be widely applied for the biosynthesis of (R)-α-lipoic acid and other metabolites.
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- Elucidating the Kinetic Mechanism of Human METTL16. [Journal Article]
- Methyltransferase-like protein 16 (METTL16) is one of four catalytically active, S-adenosylmethionine (SAM)-dependent m6A RNA methyltransferases in humans. Well-known methylation targets of METTL16 are U6 small nuclear RNA (U6 snRNA) and the MAT2A mRNA hairpins; however, METTL16 binds to other RNAs, including the 3' triple helix of the metastasis-associated lung adenocarcinoma transcript 1 (MALAT…
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- Systematic Design of Adenosine Analogs as Inhibitors of a Clostridioides difficile-Specific DNA Adenine Methyltransferase Required for Normal Sporulation and Persistence. [Journal Article]
- Antivirulence agents targeting endospore-transmitted Clostridioides difficile infections are urgently needed. C. difficile-specific DNA adenine methyltransferase (CamA) is required for efficient sporulation and affects persistence in the colon. The active site of CamA is conserved and closely resembles those of hundreds of related S-adenosyl-l-methionine (SAM)-dependent methyltransferases, which …
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- Plant homocysteine, a methionine precursor and plant's hallmark of metabolic disorders. [Review]
- Homocysteine (Hcy) is a sulfur-containing non-proteinogenic amino acid, which arises from redox-sensitive methionine metabolism. In plants, Hcy synthesis involves both cystathionine β-lyase and S-adenosylhomocysteine hydrolase activities. Thus, Hcy itself is crucial for de novo methionine synthesis and S-adenosylmethionine recycling, influencing the formation of ethylene, polyamines, and nicotian…
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- One-carbon metabolite supplementation to heifers for the first 14 days of the estrous cycle alters the plasma and hepatic one-carbon metabolite pool and methionine-folate cycle enzyme transcript abundance in a dose-dependent manner. [Journal Article]J Anim Sci. 2022 Dec 25 [Online ahead of print]JA
- The objective of this study was to determine the dose of folate and vitamin B12 in beef heifers fed rumen protected methionine and choline required to maintain increased B12 levels and intermediates of the methionine-folate cycle in circulation. Angus heifers (n = 30; BW = 392.6 ± 12.6 kg) were individually fed and assigned to one of five treatments: 0XNEG: Total mixed ration (TMR) and saline inj…
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- Circ-ERC2 Is Involved in Melatonin Synthesis by Regulating the miR-125a-5p/MAT2A Axis. [Journal Article]
- The circadian rhythm of melatonin secretion in the pineal gland is highly conserved in vertebrates. Melatonin levels are always elevated at night. Acetylserotonin O-methyltransferase (ASMT) is the last enzyme in the regulation of melatonin biosynthesis (N-acetyl-5-hydroxytryptamine-melatonin). S-adenosylmethionine (SAM) is an important methyl donor in mammals and can be used as a substrate for th…
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- The Role of the m6A RNA Methyltransferase METTL16 in Gene Expression and SAM Homeostasis. [Review]
- The RNA methylation of adenosine at the N6-position (m6A) has attracted significant attention because of its abundance and dynamic nature. It accounts for more than 80% of all RNA modifications present in bacteria and eukaryotes and regulates crucial aspects of RNA biology and gene expression in numerous biological processes. The majority of m6A found in mammals is deposited by a multicomponent c…
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- Polyamines conjugated to deoxyribonucleic acid-protein in cell nucleus from filling grain embryos were involved in tolerance of wheat to drought. [Journal Article]J Biosci. 2022; 47JB
- Deoxyribonucleic acid-protein (DNAP) of the cell nucleus was purified from developing wheat (Triticum aestivum L.) embryo cells under drought stress, with two cultivars differing in drought tolerance as experimental materials - Longmai No. 079 (drought-tolerant) and Wanmai No. 52 (drought-sensitive). Levels of polyamines (PAs) non-covalently conjugated to the DNA and covalently conjugated to the …
- Development of a synthetic transcription factor-based S-adenosylmethionine biosensor in Saccharomyces cerevisiae. [Journal Article]Biotechnol Lett. 2023 Feb; 45(2):255-262.BL
- S-Adenosylmethionine (SAM) is a crucial small-molecule metabolite widely used in food and medicine. The development of high-throughput biosensors for SAM biosynthesis can significantly improve the titer of SAM. This paper constructed a synthetic transcription factor (TF)-based biosensor for SAM detecting in Saccharomyces cerevisiae. The synthetic TF, named MetJ-hER-VP16, consists of an Escherichi…
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- Decipher the molecular evolution and expression patterns of Cupin family genes in oilseed rape. [Journal Article]Int J Biol Macromol. 2023 Feb 01; 227:437-452.IJ
- Cupin proteins are involved in plant growth and development as well as in response to various stresses. Here, a total of 173 Cupin genes were identified in Brassica napus, and their molecular evolution and expression patterns were analyzed. These genes were classified into ten groups. Motif and exon-intron structure indicated a high degree of conservation within each group during evolution. BnaCu…
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