Article
Biochemistry & Molecular Biology
Kerong Guo, Jian Li, Yingdong Jia, Xiaojuan Yang, Xiqing Yan, Liqiang Wu
Summary: In this study, novel quinolinedione-linked sulfonylpiperazine derivatives were investigated as NQO1-directed antitumor agents. Most of the compounds showed higher effectiveness in inhibiting cancer cell proliferation compared to 5-Fu and TSA. Among them, compound 22r exhibited significant anti-proliferative activity against NQO1-rich cancer cells and was recognized as an excellent substrate for NQO1. Mechanistic studies revealed that 22r induced ROS production, DNA damage, and apoptosis in HepG2 cells. Remarkably, compound 22r also showed excellent anticancer activity in HepG2 xenograft models. Overall, this study demonstrated that compound 22r could be a promising strategy for the treatment of malignant tumors.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Hongyue Yu, Yan Yu, Runfeng Lin, Minchao Liu, Qiaoyu Zhou, Mengli Liu, Liang Chen, Wenxing Wang, Ahmed A. Elzatahry, Dongyuan Zhao, Xiaomin Li
Summary: A camouflaged virus-like nanocarrier with a transformable rough surface composed of a mesoporous SiO2 nanoparticle and an acid-responsive polymer is reported. Under normal pH conditions, the spikes on the nanocarrier are hidden by the polymer shell, inhibiting non-specific strong nano-bio interactions. In an acidic tumor microenvironment, the nanocarrier sheds the polymer camouflage to expose its rough surface, improving retention ability and endocytosis efficiency. The rationally designed nanocarrier exhibits extended blood circulation time and enhanced tumor accumulation due to its dynamically variable rough surface.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Xuekang Cai, Jingming Zhang, Haishun Ye, Kai Cui, Tingting Hao, Long Yi, Xing Yang
Summary: Researchers have developed ligand-directed sensors (PSMA-Cy7-NBD and PSMA-Py-NBD) that specifically target hydrogen sulfide (H2S) and can be used in vivo. These tools exhibit high specificity and can be selectively transported into prostate cancer cells. By using them, endogenous H2S levels in tumor models can be imaged and downregulated, potentially aiding in the study of H2S cancer biology and related therapies.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Review
Medicine, General & Internal
Jin-Shou Yang, Cheng-Cheng Wang, Jiang-Dong Qiu, Bo Ren, Lei You
Summary: PDAC is an extremely malignant disease with a low survival rate, with arginine metabolism playing a crucial role in its development and progression. Arginine deprivation is considered a potential therapy, but drug resistance may develop during treatment. Arginase 1 may be a potential target for cancer immunotherapy.
CHINESE MEDICAL JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Li-Qiang Wu, Xin Ma, Zhao-Peng Liu
Summary: A series of novel NQO1-targeted anticancer agents were synthesized, with compound 5k identified as a favorable NQO1 substrate that significantly suppressed tumor growth and decreased mitochondrial membrane potential in tumor cells.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Analytical
N. Ye Stasyuk, G. Z. Gayda, A. E. Zakalskiy, L. R. Fayura, O. M. Zakalska, M. Nisnevitch, M. Gonchar
Summary: Limited data on amperometric biosensors based on deiminases that produce ammonium as a byproduct of enzymatic reaction. Novel biosensors for direct measurement of creatinine and L-arginine were successfully developed, with high sensitivities, broad linear ranges, low limits of detection, and good selectivities towards natural substrates. Real samples of biological fluids and juices were tested, showing high correlations with reference methods for the target analytes.
Article
Endocrinology & Metabolism
Mahmoud A. Mohammad, Inka C. Didelija, Barbara Stoll, Trung C. Nguyen, Juan C. Marini
Summary: ADI-PEG20 administration rapidly depletes circulating arginine while maintaining tissue concentrations, without affecting blood pressure or protein metabolism, demonstrating high citrulline turnover and regeneration of arginine through the citrulline recycling pathway.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2021)
Article
Chemistry, Analytical
Kseniia Berketa, Olga Saiapina, Lyubov Fayura, Andriy Sibirny, Sergei Dzyadevych, Oleksandr Soldatkin
Summary: A novel arginine-sensitive conductometric biosensor based on a recombinant arginine deiminase (ADI) produced in E. coli was developed for the detection of L-arginine. The biosensor exhibited high selectivity and stability, making it suitable for quantification of arginine in dietary supplements.
SENSORS AND ACTUATORS B-CHEMICAL
(2022)
Review
Oncology
Yu Zhang, Sai-Fung Chung, Suet-Ying Tam, Yun-Chung Leung, Xiao Guan
Summary: Extensive studies have shown the importance of amino acid deprivation in cancer therapy, with arginine playing a pivotal role as a key nutrient for cancer cells. Arginine deiminase and human arginase are major protein drugs used for arginine deprivation, but they face common issues in clinical applications.
Review
Chemistry, Physical
Galina Gayda, Nataliya Stasyuk, Andriy Zakalskiy, Mykhailo Gonchar, Evgeny Katz
Summary: L-Arginine is a semi-essential amino acid that plays important roles in human health. Its metabolism generates various biochemical products and it is used in clinical diagnostics, disease prevention/treatment, and quality assessment of food and beverages. Electrochemical biosensors based on Arg-degrading enzymes are considered promising tools for Arg assay.
CURRENT OPINION IN ELECTROCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Tjeerd Pols, Shubham Singh, Cecile Deelman-Driessen, Bauke F. Gaastra, Bert Poolman
Summary: The breakdown of arginine in cells generates metabolic energy in the form of ATP through a pathway consisting of specific enzymes and a transporter. Various factors such as physicochemical conditions, effector composition, and concentration can affect enzyme activity. The study provides insights into the biochemical properties of the enzymes and transporter, as well as their response to different conditions and effector concentrations.
Article
Oncology
Hui-Jen Tsai, Hui-Hua Hsiao, Ya-Ting Hsu, Yi-Chang Liu, Hsiao-Wen Kao, Ta-Chih Liu, Shih-Feng Cho, Xiaoxing Feng, Amanda Johnston, John S. Bomalaski, Ming-Chung Kuo, Tsai-Yun Chen
Summary: The combination therapy of ADI-PEG20 and low-dose cytarabine in AML patients showed promising efficacy with good tolerability, leading to an encouraging overall response rate. Further studies on this combination are warranted.
Article
Biotechnology & Applied Microbiology
Rico Schwarz, Eric Zitzow, Adina Fiebig, Silvio Hering, Yvonne Humboldt, Nina Schoenwaelder, Neele Kampfer, Kerren Volkmar, Burkhard Hinz, Bernd Kreikemeyer, Claudia Maletzki, Tomas Fiedler
Summary: The study found that conjugation of SpyADI with PEG20 significantly reduced the overall activity of the enzyme without affecting its function in arginine. Furthermore, PEGylation increased the enzyme's anti-tumor capacity against GBM cells in vitro and led to a longer-lasting reduction of plasma arginine levels in mice.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2022)
Review
Immunology
Johanna Rausch, Evelyn Ullrich, Michael W. M. Kuehn
Summary: AML is a malignant disease that is difficult to treat, especially in patients who cannot undergo intensive chemotherapy. Immunotherapy has been successful in treating solid tumors and lymphatic neoplasms, but its efficacy in AML has been limited. Epigenetic dysregulation is a driver of leukemogenesis, and combining targeted epigenetic drugs with immunotherapy may improve treatment outcomes. Further research is needed to understand the immune functions affected by these drugs and their potential for clinical use.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Jing Tian, Daniel R. Utter, Lujia Cen, Pu-Ting Dong, Wenyuan Shi, Batbileg Bor, Man Qin, Jeffrey S. McLean, Xuesong He
Summary: This study reveals the function and impact of the acquired arginine deiminase system (ADS) in Saccharibacteria during the transition from the environment to the mammalian microbiome, and demonstrates its role in the mutualistic interaction and partner selection between Saccharibacteria and host bacteria.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Agriculture, Multidisciplinary
Xiaolan Su, Jianhua Yang, Huiling Yuan, Cui Liu, Ran Tu, Pi Liu, Qinhong Wang, Leilei Zhu
Summary: Laccases are attractive biocatalysts for industry due to their broad substrate spectrum and use of oxygen as the final electron acceptor. In this study, a droplet-based microfluidic screening system was used to identify laccase variants with enhanced thermotolerance. Molecular dynamic simulations revealed that these variants had increased thermostability due to more hydrogen bonds compared to the wild type.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Biochemical Research Methods
Ruizhi Han, Ke Gao, Yulin Jiang, Jieyu Zhou, Guochao Xu, Jinjun Dong, Ulrich Schwaneberg, Yu Ji, Ye Ni
Summary: A one-pot multi-enzyme cascade pathway was developed using tyrosine aminotransferase and D-isomer-specific 2-hydroxyacid dehydrogenase to synthesize DSS from L-DOPA. Glutamate dehydrogenase was also introduced for a self-sufficient system. The pathway achieved high yields and provides a sustainable approach for DSS production.
ACS SYNTHETIC BIOLOGY
(2023)
Review
Chemistry, Multidisciplinary
Daniel F. Sauer, Ulrich Schwaneberg, Johannes Schiffels, Jun Okuda, Ulrich Schwaneberg
Summary: Protein engineering is a powerful method for tailoring protein properties, enabling the design of biohybrid catalysts and materials. The ferric hydroxamate uptake protein FhuA has been used as a versatile scaffold with a large cavity and stability towards temperature and organic solvents. Applications of FhuA have been explored in biocatalysis, materials science, and the construction of artificial metalloenzymes, showcasing its potential for creating hybrid catalysts and materials.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Lilin Feng, Liang Gao, Volkan Besirlioglu, Khalil Essani, Malte Wittwer, Tetiana Kurkina, Yu Ji, Ulrich Schwaneberg
Summary: In this study, a versatile and robust flow cytometry-based screening platform FlOxi was developed for directed oxidase evolution. FlOxi utilizes hydrogen peroxide produced by oxidases to oxidize Fe2+ and immobilize a His-tagged eGFP on the E. coli cell surface, allowing for the identification of beneficial oxidase variants. The platform was successfully validated with two oxidases and resulted in the discovery of improved variants with lower K-m values and higher k(cat) values.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Lixia Shi, Pi Liu, Zijian Tan, Wei Zhao, Junfei Gao, Qun Gu, Hongwu Ma, Haifeng Liu, Leilei Zhu
Summary: PETase exhibits high potential for PET depolymerization. However, directed evolution of PETase has been limited due to the lack of an efficient screening assay. In this study, a new fluorescence-based screening assay using a novel substrate, BHET-OH, was developed for PET hydrolases. The best variant, DepoPETase, showed significantly improved activity and stability, enabling complete depolymerization of untreated PET wastes and industrial-scale PET waste, making it a promising candidate for PET depolymerization processes. Molecular dynamic simulations revealed the molecular mechanism underlying the enhanced catalytic performance of DepoPETase.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Engineering, Biomedical
Prachi Desai, Anshuman Dasgupta, Alexandros Marios Sofias, Quim Pena, Robert Goestl, Ioana Slabu, Ulrich Schwaneberg, Thomas Stiehl, Wolfgang Wagner, Stefan Jockenhoevel, Julia Stingl, Rafael Kramann, Christian Trautwein, Tim H. Bruemmendorf, Fabian Kiessling, Andreas Herrmann, Twan Lammers
Summary: Drug delivery systems (DDS) control drug availability and activity to achieve a balance between therapeutic efficacy and side effects. They overcome biological barriers encountered by drug molecules and are explored for modulating host-material interfaces. This article provides an overview of barriers and interfaces encountered by DDS in different administration routes and highlights material engineering advances for improved disease treatment.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Biotechnology & Applied Microbiology
Zohreh N. Pourhassan, Haiyang Cui, Neele Muckhoff, Mehdi D. Davari, Sander H. J. Smits, Ulrich Schwaneberg, Lutz Schmitt
Summary: Protein secretion is advantageous for recombinant protein production. Type 1 secretion systems (T1SS) have a simple architecture and are attractive for biotechnological applications. The hemolysin A type 1 secretion system (HlyA T1SS) from Escherichia coli has been used for secretion of heterologous proteins, but its commercial utility is limited by low secretion titers. To improve this, we engineered the inner membrane complex of the system using KnowVolution strategy, resulting in a novel HlyB variant with improved secretion for two hydrolases.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Materials Science, Coatings & Films
Rahel Heesemann, Isa Bettermann, Roshan Paul, Milena Rey, Thomas Gries, Lilin Feng, Ulrich Schwaneberg, Claus Hummelsheim
Summary: The fire protection of materials is crucial in everyday life, especially in public areas such as construction and transport, electronic devices, furnishings, and textiles. The use of harmful flame retardant additives based on bromides, chlorides, phosphates, or antimony is being restricted due to their environmental and health impact. Therefore, innovative and sustainable solutions are needed to reduce the use of these additives and replace them with safer alternatives.
JOURNAL OF VACUUM SCIENCE & TECHNOLOGY A
(2023)
Article
Chemistry, Physical
Yi Lu, Kai-Wolfgang Hintzen, Tetiana Kurkina, Yu Ji, Ulrich Schwaneberg
Summary: In order to ensure a sustainable future, the responsible use of plastics in a climate-neutral and circular economy is crucial. This study focuses on developing a method to efficiently recycle bioplastic polymers, such as PLA, from petroleum-based plastics. Through the use of engineered material binding peptides, accelerated degradation of PLA in a mixed suspension of PLA and PS nanoparticles is achieved. The research identifies a specific peptide, Cg-Def, for PLA binding and develops a high-throughput screening system to enhance material-specific binding to PLA in the presence of PS. The results demonstrate improved PLA binding specificity and accelerated PLA depolymerization by fusing Cg-Def with a PLA degrading enzyme.
Article
Biochemical Research Methods
Minghui Wang, Haiyang Cui, Chenlei Gu, Anni Li, Jie Qiao, Ulrich Schwaneberg, Lihui Zhang, Junnan Wei, Xiujuan Li, He Huang
Summary: Producing bioethanol from biomass can reduce the consumption of crude oil and environmental damage. The Two-Gene Recombination Process (2GenReP) approach was used to improve the cellulase CBHI for better ethanol fermentation. The optimized CBHI variants (R2 and R4) showed enhanced ethanol resistance, solvent inhibitor tolerance, and enzymolysis stability, resulting in significantly improved ethanol yield.
ACS SYNTHETIC BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Hendrik Puetz, Christoph Janknecht, Francisca Contreras, Mariia Vorobii, Tetiana Kurkina, Ulrich Schwaneberg
Summary: A sensitive high-throughput screening system has been developed to improve the efficiency of polyamide and polyurethane recycling by tailoring polyamidases through directed depolymerase evolution. With global polymer production set to exceed 400 megatons annually, the development of recycling methods that enable a climate-neutral, circular polymer economy is crucial to address environmental pollution and climate change. This study presents the first validated high-throughput screening system for optimizing polyamidases in polyamide degradation, enabling the detection of degradation products in cell-free extract and resulting in a 1.9-fold increase in turnover frequency with just one round of random mutagenesis.
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
(2023)
Article
Chemistry, Multidisciplinary
Yi Lu, Kai-Wolfgang Hintzen, Tetiana Kurkina, Yu Ji, Ulrich Schwaneberg
Summary: Polylactic acid (PLA) is considered as a promising biopolymer to replace petrochemical-based polymers and is often blended with other polymers like polypropylene (PP) for improved properties. A technical challenge in recycling PLA/PP blends is the separation of PLA from PP. This study reports the development of a protein engineering approach to improve the material-specific binding of PLA by designing material binding peptides (MBPs) and successfully obtaining a variant with 2.3-fold improved PLA binding specificity compared to PP. The established screening platform provides a general methodology for designing material-specific MBPs for applications in PLA detection, sorting, and degradation in mixed plastics.
Article
Biochemistry & Molecular Biology
Lixia Shi, Leilei Zhu
Summary: This article discusses the mechanisms, challenges, and factors affecting the enzymatic depolymerization of PET, as well as protein engineering approaches to improve depolymerization performance. Additionally, it explores the opportunities and challenges in bio-recycling and bio-upcycling of PET wastes.
Article
Agriculture, Multidisciplinary
Nan Zhang, Jianhua Yang, Zhimin Li, Junaid Haider, Yingying Zhou, Yu Ji, Ulrich Schwaneberg, Leilei Zhu
Summary: This study systematically investigated the influence of four new carbohydrate-binding modules (CBMs) on the performance of starch-active AA13 lytic polysaccharide monooxygenases (LPMOs). The results showed that CBMs greatly enhanced the substrate binding, H2O2 production activity, and oxidative product yields of the AA13 LPMOs. These findings are important for understanding the role of CBMs in starch degradation.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
