Article
Chemistry, Multidisciplinary
Xuan Fu, Madhusudhan Reddy Gadi, Shuaishuai Wang, Jinghua Han, Ding Liu, Xi Chen, Jun Yin, Lei Li
Summary: Accessing structurally diverse glycans is crucial for functional glycomics. Our study demonstrates the general tolerance of galactosyltransferases towards UDP-GalN, enabling the synthesis of novel GalNAc-glycosides. This discovery expands the catalytic capabilities of glycosyltransferases, facilitating the synthesis of diverse glycans and glycoconjugates for biological studies.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Multidisciplinary Sciences
Mathias Nielsen, Noortje de Haan, Weston Kightlinger, Zilu Ye, Sally Dabelsteen, Minyan Li, Michael C. Jewett, Ieva Bagdonaite, Sergey Y. Vakhrushev, Hans H. Wandall
Summary: This study systematically analyzed the isoform-specific targets of all GalNAc-Ts expressed in skin cells, revealing the biological effects of O-glycan initiation on epithelial formation. Over 300 unique glycosylation sites were identified on a diverse set of proteins, regulated by specific GalNAc-T isoforms, highlighting their impact on tissue phenotypes. The variability in O-glycosylation site-occupancy of secreted proteins suggests the importance of individual O-glycosylation sites in driving biological functions.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Qing Chen, Xunju Liu, Yueyang Hu, Yan Wang, Bo Sun, Tao Chen, Ya Luo, Yong Zhang, Mengyao Li, Zejing Liu, Xiaorong Wang, Haoru Tang
Summary: In this study, cloning and functional characterization of a UGT, UGT78H2 in blackberry fruits was reported. The UGT78H2 was found to predominantly glycosylate quercetin and exhibit higher catalytic efficiency towards UDP-galactose.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Oncology
Emma C. Hulshof, Mirjam de With, Femke M. de Man, Geert-Jan Creemers, Birgit A. L. M. Deiman, Jesse J. Swen, Saskia Houterman, Stijn L. W. Koolen, Sander Bins, Anna M. J. Thijs, Marjan M. J. Laven, Anke M. Hovels, Saskia A. C. Luelmo, Danny Houtsma, Katerina Shulman, Howard L. McLeod, Ron H. N. van Schaik, Henk-Jan Guchelaar, Ron H. J. Mathijssen, Hans Gelderblom, Maarten J. Deenen
Summary: This study aimed to determine the safety, feasibility, pharmacokinetics, and cost of UGT1A1 genotype-guided dosing of irinotecan. The results showed that UGT1A1 genotype-guided dosing significantly reduces the incidence of febrile neutropenia in UGT1A1 PM patients treated with irinotecan, results in a therapeutically effective systemic drug exposure, and is cost-saving.
EUROPEAN JOURNAL OF CANCER
(2022)
Review
Biochemistry & Molecular Biology
Ellie-May Beaman, David R. F. Carter, Susan A. Brooks
Summary: The UDP-N-alpha-D galactosamine:polypeptide N-acetylgalactosaminyltransferases family (ppGalNAc-Ts, GalNAc-Ts or GALNTs) is responsible for the initial synthesis of Tn antigen in mucin type O-linked glycosylation. Changes in GALNT expression have been extensively reported in various cancers and can affect glycosylation and cancer progression.
Article
Microbiology
Guosi Li, Fucheng Zhu, Peipei Wei, Hailong Xue, Naidong Chen, Baowei Lu, Hui Deng, Cunwu Chen, Xinjian Yin
Summary: Hyperoside, a compound with higher bioactivities than quercetin, was efficiently synthesized from quercetin by co-expressing UGT from Petunia hybrida and GalE in E. coli. Additional enzymes Pgm and GalU were introduced to enhance UDP-glucose synthesis, leading to improved hyperoside production. Through fermentation optimization, hyperoside production was increased, and substrate-fed batch fermentation further increased production to 831.6 mg/L with a high conversion ratio and specific productivity. This efficient pathway can be applied for glycosylation of other flavonoids and bioactive substances.
Article
Chemistry, Medicinal
Katarina Grabrijan, Martina Hrast, Matic Proj, Ana Dolsak, Irena Zdovc, Timea Imre, Laszlo Petri, Peter Abranyi-Balogh, Gyorgy M. Keseru, Stanislav Gobec
Summary: The study focused on the development of new antibacterial agents by inhibiting the enzyme MurA. A potent compound with potential antibacterial activity was identified, providing a valuable starting point for the development of new antibiotics.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Kentaro Kato, Lars Hansen, Henrik Clausen
Summary: Mucin-type O-glycosylation involves the attachment of glycans to an initial O-linked N-acetylgalactosamine (GalNAc) on serine and threonine residues on proteins. This process in mammals is initiated and regulated by a large family of 20 UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) (EC 2.4.1.41). Two of these genes, GALNT2 and GALNT3, are known as monogenic autosomal recessive inherited disease genes with well characterized phenotypes, whereas a broad spectrum of phenotypes is associated with the remaining 18 genes. Until recently, the overlapping functionality of the 20 members of the enzyme family has hindered characterizing the specific biological roles of individual enzymes. However, recent evidence suggests that these enzymes do not have full functional redundancy and may serve specific purposes that are found in the different phenotypes described. Here, we summarize the current knowledge of GALNT and associated phenotypes.
Review
Biotechnology & Applied Microbiology
Peixin Liang, Mingfeng Cao, Jing Li, Qinhong Wang, Zongjie Dai
Summary: Sugar alcohols are widely used in chemical, pharmaceutical, and food production. The traditional chemical synthesis of polyols is complex and involves the use of hazardous compounds. Microbe-mediated production of polyols has been proposed as an alternative strategy. This review focuses on the metabolic engineering strategies and low-cost substrates for the production of four representative sugar alcohols, as well as the challenges and future development in broadening the application of sugar alcohols.
BIOTECHNOLOGY ADVANCES
(2023)
Article
Biochemistry & Molecular Biology
Elisabeth Kurze, Victoria Russ, Nadia Syam, Isabelle Effenberger, Rafal Jonczyk, Jieren Liao, Chuankui Song, Thomas Hoffmann, Wilfried Schwab
Summary: Research has identified five enzymes from the tea plant that can be used for the biotechnological production of menthyl glucoside, with UGT93Y1 showing the highest catalytic activity. This discovery opens up new possibilities for the synthesis of menthyl glucoside, offering potential applications in various industries.
Article
Biochemistry & Molecular Biology
Shuen-Shiuan Wang, Virginia del Solar, Xinheng Yu, Aristotelis Antonopoulos, Alan E. Friedman, Kavita Agarwal, Monika Garg, Syed Meheboob Ahmed, Ahana Addhya, Mehrab Nasirikenari, Joseph T. Lau, Anne Dell, Stuart M. Haslam, Srinivasa-Gopalan Sampathkumar, Sriram Neelamegham
Summary: Ac(5)GalNTGc is an effective inhibitor of O-glycosylation, truncating O-glycan biosynthesis in leukocytes and cells. It mainly affects O-glycans, with minimal impact on N-glycans and glycosphingolipids. In mouse experiments, Ac(5)GalNTGc showed potential in reducing leukocyte infiltration to sites of inflammation.
CELL CHEMICAL BIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Igor A. Podolsky, Susanna Seppala, Haiqing Xu, Yong-Su Jin, Michelle A. O'Malley
Summary: The study identified a novel fungal SWEET transporter, NcSWEET1, from anaerobic fungi that can enhance glucose and xylose co-utilization. By constructing single cross-over chimeras and studying protein structure and function, enhanced variants were identified, offering potential applications in improving sugar transport efficiency.
METABOLIC ENGINEERING
(2021)
Article
Chemistry, Multidisciplinary
Pablo G. Argudo, Lea Spitzer, Francois Jerome, Henri Cramail, Luis Camacho, Sebastien Lecommandoux
Summary: Sugar-based amphiphiles are a natural alternative to synthetic ones with biodegradable properties. An investigation of their structure-assembly relationship was conducted using various techniques in aqueous media. The results showed that the average degree of polymerization (DP) and the addition of a hydroxyl group to the hydrophobic tail affected their self-assembly. The critical micelle concentration was more influenced by changes in the hydrophobic molecular region than by variations in (DP) over bar. Amphiphiles with high (DP) over bar formed spherical micelles regardless of the presence of a hydroxyl group, while those with low (DP) over bar and only one hydrophilic moiety formed cylindrical micelles, and the addition of a hydroxyl group to the tail resulted in a spherical shape.
Article
Mathematics
Ramlal Debnath, Deepak K. Pradhan, Jaydeb Sarkar
Summary: This paper investigates the classification of inner projections and their relationships with other problems. Two independent applications are presented as well.
JOURNAL OF FUNCTIONAL ANALYSIS
(2024)
Article
Chemistry, Multidisciplinary
Ruben A. Fritz, Yamil J. Colon, Felipe Herrera
Summary: The study investigates the potential applications of metal-organic framework crystals in optical quantum technology, highlighting the need for scalable computational assessment tools to accelerate materials discovery.
Article
Biochemistry & Molecular Biology
Daniela J. Carroll, Mary W. N. Burns, Lynda Mottrarn, Daniel C. Propheterl, Andrew Boucher, Gabrielle M. Lessen, Ashwani Kumar, Stacy A. Malaker, Chao Xing, Lora Hooper, Ulf Yrlid, Jennifer J. Kohler
Summary: IL-22 signaling regulates fucosylation of glycoproteins in intestinal epithelial cells by regulating the expression of B3GNT7, which is involved in the synthesis of polyLacNAc chains. This study uncovers a novel role for B3GNT7 in intestinal fucosylation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Chemistry, Organic
Hee Jin Jeong, Ji Ho Kim, Jae Kyun Lee, Hyo Jae Yoon, Junwon Choi, Seo-Jung Han
Summary: An efficient and transition-metal-free three-component reaction was developed for the synthesis of benzoxaphosphole 1-oxides. This reaction is useful for preparing organophosphorus compounds encountered in natural products and materials.
Review
Biochemistry & Molecular Biology
Deniz Ince, Taryn M. Lucas, Stacy A. Malaker
Summary: Glycosylation, especially O-linked glycosylation, is still a blind spot in understanding post-translational modifications. Mucins, which are defined by a large density and abundance of O-glycosylation, present extra challenges in their analysis. However, recent breakthroughs in various areas have made mucin-domain glycoproteins more accessible for study. This includes the use of mucinases in glycoproteomic workflows, manipulation of cellular glycosylation pathways, and advances in synthetic methods to mimic mucin domains.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Suzanne B. P. E. Timmermans, Alireza Ramezani, Toni Montalvo, Mark Nguyen, Paul van der Schoot, Jan C. M. van Hest, Roya Zandi
Summary: This study reports on the spontaneous and reversible size conversion of empty capsids of CCMV, which is mediated by a hydrophobic elastin-like polypeptide and pH jump. The conversion process from T = 1 to T = 3 is 10 times slower than that from T = 3 to T = 1. The experimental findings are explained using a simple model based on classical nucleation theory.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Multidisciplinary Sciences
Stacy A. Malaker, Nicholas M. Riley, D. Judy Shon, Kayvon Pedram, Venkatesh Krishnan, Oliver Dorigo, Carolyn R. Bertozzi
Summary: This study presents a technique for selectively enriching and characterizing mucin-domain glycoproteins from cell lysate and patient biofluids. The authors demonstrate the effectiveness of this technique in detecting and identifying a large number of mucin-domain glycoproteins.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Brendon J. Medley, Leif Leclaire, Nicole Thompson, Keira E. Mahoney, Benjamin Pluvinage, Matthew A. H. Parson, John E. Burke, Stacy Malaker, Warren Wakarchuk, Alisdair B. Boraston
Summary: Akkermansia muciniphila, a key member of the human gut microbiota, has a significant impact on host health through its interaction with host mucin. This study identifies an uncharacterized protein, AMUC_1438, as a unique O-glycopeptidase with mucin-degrading capacity. The protein has a metzincin metalloprotease catalytic motif and specifically recognizes a GalNAc residue alpha-linked to serine or threonine. This understanding of the protein's structure and function contributes to the broader understanding of O-glycopeptidase enzymes and their role in host adaptation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Medicine, General & Internal
Chi-Hoon Oh, Junhyun Kim, Junhan Kim, Siyeong Yoon, Younghoon Jung, Hyun Il Lee, Junwon Choi, Soonchul Lee, Soo-Hong Han
Summary: This study investigated the correlation between distal radius fractures (DRF) and low skeletal muscle mass, and found that female sex, cardiovascular disease (CVD), and low skeletal muscle mass were significant predictors for DRF, while BMI and osteoporosis were not significantly related.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Medicine, General & Internal
Hyun-Ju An, Jae-Hwa Kim, Siyeong Yoon, Junwon Choi, Jeongmo Koo, Soonchul Lee
Summary: This study aimed to identify specific genes or genetic variants associated with rotator cuff tears through a genome-wide association study. More than 20 significantly associated SNPs were found. However, the study was limited by the small sample size and requires further validation. Nevertheless, the identification of potential genetic variants related to rotator cuff injury would aid in the early detection of individuals at risk and provide insight into future gene therapies.
Review
Chemistry, Multidisciplinary
Junwon Choi
Summary: This review discusses the role of ENPP1 in innate immunity and its application as an immunomodulator in cancer immunotherapy, particularly as an ENPP1 inhibitor.
BULLETIN OF THE KOREAN CHEMICAL SOCIETY
(2023)
Article
Biotechnology & Applied Microbiology
Kayvon Pedram, D. Judy Shon, Gabrielle S. Tender, Natalia R. Mantuano, Jason J. Northey, Kevin J. Metcalf, Simon P. Wisnovsky, Nicholas M. Riley, Giovanni C. Forcina, Stacy A. Malaker, Angel Kuo, Benson M. George, Caitlyn L. Miller, Kerriann M. Casey, Jose G. Vilches-Moure, Michael J. Ferracane, Valerie M. Weaver, Heinz Laeubli, Carolyn R. Bertozzi
Summary: Targeted protein degradation can suppress cancer in mice by eliminating undruggable proteins. In this study, degraders were designed to selectively degrade mucins, glycosylated proteins that drive cancer progression, by recognizing specific peptide and glycan motifs and binding to cell surfaces. The engineered protease, fused with a cancer antigen-binding nanobody, degraded mucins on cancer cells, induced cell death, and reduced tumor growth in mouse models of breast cancer. This research provides a blueprint for developing biologics that degrade specific protein glycoforms on target cells.
NATURE BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Joann Chongsaritsinsuk, Alexandra D. Steigmeyer, Keira E. Mahoney, Mia A. Rosenfeld, Taryn M. Lucas, Courtney M. Smith, Alice Li, Deniz Ince, Fiona L. Kearns, Alexandria S. Battison, Marie A. Hollenhorst, D. Judy Shon, Katherine H. Tiemeyer, Victor Attah, Catherine Kwon, Carolyn R. Bertozzi, Michael J. Ferracane, Mark A. Lemmon, Rommie E. Amaro, Stacy A. Malaker
Summary: This study investigates the structure and function of mucin glycoproteins. By using the mucinase SmE for mass spectrometric analysis, the researchers successfully overcome the challenges associated with studying mucin domains. They also employ molecular dynamics simulations and binding assays to gain a deeper understanding of how glycosylation controls protein structure and function.
NATURE COMMUNICATIONS
(2023)
Letter
Biochemistry & Molecular Biology
Michael Boyce, Stacy A. Malaker, Nicholas M. Riley, Jennifer J. Kohler
Article
Medicine, General & Internal
Kyeongmi Kim, Siyeoung Yoon, Junwon Choi, Soonchul Lee
Summary: This study investigated the effect of the duration of non-steroidal anti-inflammatory drugs (NSAIDs) use on COVID-19 infection and clinical outcomes. The results showed that the duration of NSAIDs use did not have a statistically significant effect on COVID-19 infectivity or clinical outcomes. However, further studies with a larger sample size are needed to examine clinical presentation and laboratory test results.
MEDICINA-LITHUANIA
(2022)
Review
Multidisciplinary Sciences
Ieva Bagdonaite, Stacy A. Malaker, Daniel A. Polasky, Nicholas M. Riley, Katrine Schjoldager, Sergey Y. Vakhrushev, Adnan Halim, Kiyoko F. Aoki-Kinoshita, Alexey I. Nesvizhskii, Carolyn R. Bertozzi, Hans H. Wandall, Benjamin L. Parker, Morten Thaysen-Andersen, Nichollas E. Scott
Summary: This Primer provides an overview of glycoproteomic methods and their applications, including glycopeptide analysis, sample selection, and mass spectrometry techniques. It focuses on the study of N-linked and O-linked glycosylation and provides insights into future directions in the field.
NATURE REVIEWS METHODS PRIMERS
(2022)
Article
Biochemistry & Molecular Biology
Stacy Alyse Malaker, Jusal Quanico, Antonella Raffo-Romero, Firas Kobeissy, Soulaimane Aboulouard, Dominique Tierny, Carolyn Ruth Bertozzi, Isabelle Fournier, Michel Salzet
Summary: In this study, we propose an approach combining MALDI N-glycan mass spectrometry imaging (MSI) with spatially resolved glycoproteomics to identify N-linked glycoproteins and deduce their spatial localization. The experiments conducted on glioma biopsies revealed the predominant expression of a specific glycan in necrotic regions of high-grade canine gliomas, which was further linked to a specific protein through manual glycoproteomic analysis. Our spatially resolved glycoproteomics technique successfully identified over 400 glycopeptides from various proteins, demonstrating the diversity of glycosylation on tissue slices and the sensitivity of the technique.
CELL CHEMICAL BIOLOGY
(2022)