Article
Multidisciplinary Sciences
Eunah Jeong, Wonyong Kim, Seungju Son, Sungyeon Yang, Dasom Gwon, Jihee Hong, Yoonhee Cho, Chang-Young Jang, Martin Steinegger, Young Woon Lim, Kyo Bin Kang
Summary: Wood-decaying fungi have the potential to produce versatile enzymes for detoxifying antifungal phytochemicals. In this study, a mass spectrometry-based untargeted metabolomics pipeline was developed to analyze fungal cultures treated with antifungal plant phenolics, leading to the identification of a UDP-glycosyltransferase enzyme with broad substrate specificity. This workflow will facilitate the characterization of fungal enzymes as biocatalysts.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Pharmacology & Pharmacy
Hui-Yao Gao, Yan Liu, Fei-Fan Tan, Li-Wen Zhu, Kai-Zhi Jia, Ya-Jie Tang
Summary: This study discusses the mining of C-glycosyl flavones and the corresponding C-glycosyltransferases, and evaluates the differences in structure and catalytic mechanisms between C-glycosyltransferase and O-glycosyltransferase. The research concludes that promiscuity and specificity are key determinants for general flavonoid C-glycosyltransferase engineering and summarizes the C-glycosyltransferase engineering strategy. A thorough understanding of the properties, catalytic mechanisms, and engineering of C-glycosyltransferases will be critical for future biotechnological applications in areas such as the production of desired C-glycosyl flavonoids for nutritional or medicinal use.
CURRENT PHARMACEUTICAL DESIGN
(2022)
Article
Chemistry, Multidisciplinary
Peng Zhang, Yu Ji, Shuaiqi Meng, Zhongyu Li, Dennis Hirtz, Lothar Elling, Ulrich Schwaneberg
Summary: The PhyloDirect approach, combining directed evolution and phylogenetic mining, improves the catalytic efficiency of GT BarGT-3 and expands its substrate range, offering new opportunities for the development and application of efficient biocatalysts in green chemistry and other industrial processes.
Article
Microbiology
Yang-Yang Li, Rong-Jun Cai, Jia-Ying Yang, Tamara L. Hendrickson, Ye Xiang, Babak Javid
Summary: Most bacteria use a two-step indirect pathway to aminoacylate tRNA(Gln) and tRNA(Asn), despite its higher energy consumption and error-prone nature. Translational errors in mycobacteria allow adaptation to hostile environments, such as antibiotic treatment, by generating novel proteins not coded by the genome. Clinical mutations in gatA dysregulate the indirect pathway in Mycobacterium tuberculosis, leading to increased mistranslation rates. Increasing stability of the GatCAB complex improves translational fidelity in both wild-type and mutant bacteria, suggesting a mechanism for tuning mistranslation rates.
Article
Agriculture, Multidisciplinary
Zhen Xu, Li-Li Hong, Chun-Sheng Liu, Jian-Qiang Kong
Summary: In this study, Quercetin 3-O-N-acetylgalactosamine (Q3GalNAc), a compound that had never been enzymatically synthesized before, was successfully produced. The enzyme PhUGT was identified to have quercetin GalNAc-T activity and was engineered to enhance the conversion rate. The study also revealed the donor promiscuity of PhUGT and provided a potent biocatalyst for glycodiversifying quercetin.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Alexander Kroll, Sahasra Ranjan, Martin K. M. Engqvist, Martin J. Lercher
Summary: For most proteins annotated as enzymes, it is unknown which primary and/or secondary reactions they catalyze. Machine learning predictions could provide an efficient alternative, but are hampered by a lack of information regarding enzyme non-substrates, as available training data comprises mainly positive examples. Here, we present ESP, a general machine-learning model for the prediction of enzyme-substrate pairs with an accuracy of over 91% on independent and diverse test data.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Jianhua Wei, Xuan Zhang, Yucong Zhou, Xingnuo Cheng, Zhi Lin, Mancheng Tang, Jianting Zheng, Binju Wang, Qianjin Kang, Linquan Bai
Summary: This study presents the molecular structure of ansamycin-modifying carbamoyltransferase GdmN and demonstrates its redesign into an iterative enzyme. Carbamoyltransferases are important enzymes that can improve the atom economy and diversity of industrial enzymatic processes. Through structural and computational analysis, the researchers successfully engineered an iterative carbamoyltransferase capable of successive carbamoylation reactions. This study reveals a subclade of the carbamoyltransferase family and showcases the potential of protein engineering for generating iterative enzymes.
NATURE COMMUNICATIONS
(2022)
Review
Biochemical Research Methods
Joong-Hoon Ahn, Yoojin Chong, Shin -Won Lee
Summary: Plants produce various types of phenolic compounds, and the biological importance of phenolic C-glycosides has led to the exploration of their synthesis. Different classes of C-glycosyltransferases have been identified and classified based on the type of sugar acceptor. Recent progress in the development and application of these enzymes in microbial systems has enabled the synthesis of phenolic C-glycosides.
CURRENT OPINION IN BIOTECHNOLOGY
(2022)
Article
Biology
Shuangzhi Yuan, Yong Sun, Wenqiang Chang, Jiaozhen Zhang, Jifa Sang, Jiachun Zhao, Minghui Song, Yanan Qiao, Chunyang Zhang, Mingzhu Zhu, Yajie Tang, Hongxiang Lou
Summary: Herbivores have evolved detoxification mechanisms for feed components. Silkworms that feed on Cudrania tricuspidata leaves (CTLs) have smaller bodies, slower growth, and lower silk production compared to those fed mulberry leaves. The high content of prenylated isoflavones (PIFs) in CTLs is converted into glycosylated derivatives (GPIFs) in silkworm faeces through gut microbiota, and this biotransformation is essential for PIFs detoxification. Adding Bacillus subtilis as a probiotic can improve gut microbiota and promote silkworm growth and development.
COMMUNICATIONS BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Hanqing Xie, Fengxi Li, Yaning Xu, Chunyu Wang, Yuelin Xu, Junhao Wu, Zhengqiang Li, Zhi Wang, Lei Wang
Summary: We present a hemoglobin-catalyzed strategy for the highly stereoselective synthesis of nitrile-substituted cyclopropanes. This method utilizes an asymmetric olefin cyclopropanation reaction catalyzed by wild-type Vitreoscilla hemoglobin in the presence of in situ generated diazoacetonitrile, offering efficiency and environmental friendliness. This sustainable approach allows for efficient synthesis of various chiral nitrile-substituted cyclopropanes and expands the practical application of hemoglobin in organic synthesis.
Article
Chemistry, Medicinal
Esther Heid, Samuel Goldman, Karthik Sankaranarayanan, Connor W. Coley, Christoph Flamm, William H. Green
Summary: Data-driven computer-aided synthesis planning using organic or biocatalyzed reactions has led to the development of tools like EHreact, which can extract and score reaction rules without expert knowledge, improving accuracy and functionality.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Chemistry, Organic
Zhongyu Wan, Quan-De Wang, Dongchang Liu, Jinhu Liang
Summary: Enzyme-catalyzed synthesis reactions play a crucial role in various applications, and accurately predicting the optimal conditions for these reactions is challenging. By combining a data-driven machine learning model with reactivity descriptors, this study achieved successful prediction of optimal reaction conditions using a Quadratic support vector machine model. The proposed method is applicable to a wide range of chemical reactions and provides efficient optimization for organic synthesis reactions.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Marc Caballe, Magda Faijes, Antoni Planas
Summary: Glycolipids, a type of complex molecule involved in important cellular processes, have attracted attention in biomedicine due to the immunostimulatory capabilities of a glycosphingolipid called alpha-galactosylceramide. Researchers have identified an enzyme, called ceramide glycosyltransferase, capable of synthesizing this glycolipid under specific conditions. Further protein engineering may enhance the stability and activity of this enzyme for the enzymatic synthesis of alpha-GalCer in biomedical applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Maxim P. Nikitin
Summary: The discovery of the DNA double helix has revolutionized our understanding of data processing in living systems. This study reveals a phenomenon called "strand commutation," which is a fundamentally different mechanism of information storage and processing by DNA/RNA based on reversible low-affinity interactions of non-complementary nucleic acids. The researchers demonstrate this mechanism by constructing a memory circuit and simulating an AND gate with high input capacity, as well as algebraic systems with changing variables. The study also identifies potential pathways of gene regulation with non-complementary strands, which could be key to reducing off-target therapeutic effects.
Article
Chemistry, Organic
Shuang Liu, Meng Zhang, Yangoujie Bao, Kuan Chen, Lulu Xu, Huifei Su, Yi Kuang, Zilong Wang, Xue Qiao, Min Ye
Summary: A novel 2''-O-galactosyltransferase TcOGT4 was discovered from Trollius chinensis, which could specifically catalyze the 2''-O-galactosylation of 17 flavone 8-C-beta-D-glucosides and showed high preference for UDP-Gal. Molecular docking suggested that Pro361 may play a key role in sugar donor selectivity. The study obtained a total of 21 products, including 17 new compounds, and 5 of them exhibited potent COX-2 inhibitory activities.
Article
Chemistry, Multidisciplinary
Mohammad Murshid Alam, Cassie M. Jarvis, Robert Hincapie, Craig S. McKay, Jiri Schimer, Carlos A. Sanhueza, Ke Xu, Roger C. Diehl, M. G. Finn, Laura L. Kiessling
Summary: DC surface lectins recognize glycans not typically present on host tissue to facilitate antigen uptake and presentation. Signal transduction through DC-SIGN depends on the ligand displayed on the VLP, promoting DC maturation and induction of a T(H)1-type immune response.
Editorial Material
Biochemistry & Molecular Biology
Laura L. Kiessling
ACS CHEMICAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Yusuke Fujiwara, Yuki Yamanashi, Akiko Fujimura, Yuko Sato, Tomoya Kujirai, Hitoshi Kurumizaka, Hiroshi Kimura, Kenzo Yamatsugu, Shigehiro A. Kawashima, Motomu Kanai
Summary: The study developed a chemical catalyst that can achieve histone acetylation in living cells without genetic manipulation, offering a new tool for studying epigenetic regulation. This chemical method competes with and suppresses normal chromatin function markers, providing insights into epigenetic mechanisms.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Organic
Kazuki Takahashi, Akira Sugiyama, Kei Ohkubo, Toshifumi Tatsumi, Tatsuhiko Kodama, Kenzo Yamatsugu, Motomu Kanai
Summary: A new axially substituted SiPc payload that is more easily synthesized was reported, showing light- and antigen-dependent cytotoxicity in HER2-overexpressing cancer cell lines when conjugated with Trastuzumab.
Article
Chemistry, Organic
Kenzo Yamatsugu, Shigehiro A. Kawashima, Kenzo Yamatsugu, Motomu Kanai
Summary: This study presents a one-step synthesis of phosphodiesters from alcohols using phosphoenolpyruvate phosphodiesters as phosphoryl donors. The method allows for the use of various functionalized alcohols as substrates and holds potential applications in diverse fields including biology and medicine.
Article
Chemistry, Multidisciplinary
Jordan S. Ho, Amira Gharbi, Baptiste Schindler, Oznur Yeni, Richard Bredy, Laurent Legentil, Vincent Ferrieres, Laura L. Kiessling, Isabelle Compagnon
Summary: Sequencing glycans is challenging due to their structural diversity. In this study, researchers used infrared multiple photon dissociation spectroscopy with mass spectrometry to differentiate between pyranose- and furanose-linked galactose residues, offering a solution to distinguish between these isomers. By analyzing hexose ammonium adducts, the researchers determined diagnostic MS-IR signatures of galactose anomers in different forms, demonstrating the utility of MS-IR for analyzing unique substructures in bacterial glycans.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Christopher Adamson, Hidetoshi Kajino, Shigehiro A. Kawashima, Kenzo Yamatsugu, Motomu Kanai
Summary: The study presents a boronate-assisted hydroxamic acid (BAHA) catalyst system for introducing protein post-translational modifications within living cells, demonstrating potential for diverse and new-to-nature PTMs. The catalyst utilizes a local molarity effect to promote acyl transfer to target residues, with micromolar reagent concentrations and minimal off-target protein reactivity. Additionally, the BAHA catalyst system is resistant to glutathione, enabling abiotic chemistry efforts within living cells.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Review
Biochemistry & Molecular Biology
Laura L. Kiessling, Roger C. Diehl
Summary: The text discusses how proteins recognize sugars through CH-π interactions, highlighting the importance of electron-rich aromatic residues in glycan binding.
ACS CHEMICAL BIOLOGY
(2021)
Editorial Material
Biochemistry & Molecular Biology
Mia L. Huang, Laura L. Kiessling
ACS CHEMICAL BIOLOGY
(2021)
Editorial Material
Biochemical Research Methods
Amanda E. Dugan, Amanda L. Peiffer, Laura L. Kiessling
Summary: Interactions between carbohydrates and lectins play a key role in viral infection. Studying glycosylation has been challenging, but recent advancements in methods have allowed for atomic-level information about glycans on viruses and host cells.
Article
Biochemical Research Methods
Kenzo Yamatsugu, Hiroto Katoh, Takefumi Yamashita, Kazuki Takahashi, Sho Aki, Toshifumi Tatsumi, Yudai Kaneko, Takeshi Kawamura, Mai Miura, Masazumi Ishii, Kei Ohkubo, Tsuyoshi Osawa, Tatsuhiko Kodama, Shumpei Ishikawa, Motomu Kanai, Akira Sugiyama
Summary: Antibody-drug conjugates (ADCs) are important therapeutic tools for advanced cancer treatment. However, the development of ADCs is hindered by manufacturing issues and the complexity of payload conjugation. This study introduces antibody mimetic-drug conjugates (AMDCs) which utilize the non-covalent binding property of payloads to target multiple molecules, providing rapid, stable, and high-yield therapeutics against multiple targets.
PROTEIN EXPRESSION AND PURIFICATION
(2022)
Article
Biochemical Research Methods
Elad Deiss-Yehiely, Spencer D. Brucks, Natalie Boehnke, Andrew J. Pickering, Laura L. Kiessling, Paula T. Hammond
Summary: Targeted delivery of nanoparticle drug carriers is crucial for the development of nanomedicine. In this study, the authors investigated the association between modified nanoparticles and ovarian cancer cells using the well-characterized hyaluronic acid-CD44 binding pair. The results demonstrated that functionalizing nanoparticles with high molecular weight hyaluronic acid using the layer-by-layer adsorption method improved cell association.
BIOCONJUGATE CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Azin Saebi, Joseph S. Brown, Victoria M. Marando, Nina Hartrampf, Nicole M. Chumbler, Stephanie Hanna, Mackenzie Poskus, Andrei Loas, Laura L. Kiessling, Deborah T. Hung, Bradley L. Pentelute
Summary: The impermeable outer membrane of Pseudomonas aeruginosa can be bypassed by antibacterial proteins called S-type pyocins. Pyocins are investigated as a potential new class of antimicrobials against Pseudomonas infections due to their properties. In this study, a rapid production method for a pyocin S2 import domain was employed using automated fast-flow peptide synthesis, resulting in milligram quantities of the desired product. These synthetic pyocin domains can be used to understand the import mechanisms of P. aeruginosa and to develop selective antimicrobial agents that can bypass the outer membrane.
ACS CHEMICAL BIOLOGY
(2023)
Review
Chemistry, Multidisciplinary
Kenzo Yamatsugu, Motomu Kanai
Summary: Carbohydrates, as fundamental units in biological processes, play pivotal roles. Developing methods for synthesizing, functionalizing, and manipulating carbohydrates is essential for understanding their functions and creating sugar-based functional materials. New approaches to site-selective transformations of carbohydrates are of great significance for revolutionizing sugar chemistry and accessing sugars of interest.
Article
Chemistry, Multidisciplinary
Katherine I. Taylor, Jordan S. Ho, Hallie O. Trial, Alan W. Carter, Laura L. Kiessling
Summary: Probes that covalently label protein targets are crucial for identifying ligand-binding sites. Squaramides, as mild electrophiles, exhibit higher selectivity for binding site lysine residues, making them promising for affinity-based chemoproteomic probes.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)