Article
Chemistry, Physical
Alessandra G. Ritacca, Anna Rovaletti, Giorgio Moro, Ugo Cosentino, Ulf Ryde, Emilia Sicilia, Claudio Greco
Summary: This study proposes a novel mechanism for the oxidation of CO into CO2 by Mo/Cu CO dehydrogenase, and explores the role of a stable thiocarbonate intermediate. The findings suggest that the thiocarbonate does not interfere with the CO oxidation catalytic cycle, highlighting the importance of environmental effects in computational modeling.
Article
Chemistry, Multidisciplinary
Rakesh Kumar Tiwari, Vinayak Pandey, Harshita Srivastava, Ambrish Kumar Srivastava, Vishnudatt Pandey
Summary: The hydrophobic residues Gly 81, Phe 133, and Ile 147 in the interface between the MTase domain and RdRp of NS5 protein may play a key role in stabilizing the crucial residues involved in enzymatic activity.
FRONTIERS IN CHEMISTRY
(2023)
Article
Endocrinology & Metabolism
Qimi Zheng, Chunxiao Yan, Nana Lv, Hengping Pu, Fatemeh Mollaamin, Majid Monajjemi
Summary: This study aims to understand the essential concepts of the Omicron variant and its effectiveness in existing vaccines. The results show that asafoetida can be used in the treatment of Omicron subvariants BA.4 and BA.5 by adsorbing its effective compound of ferulic acid on the surface of (6,6) armchair SWCNT. The physico-chemical properties of NMR, IR, and UV-VIS spectroscopy support the feasibility of this drug delivery system.
JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS
(2023)
Article
Biochemistry & Molecular Biology
Mohsen Sargolzaei, Hossein Nikoofard
Summary: In this study, we designed a suitable ester prodrug of omapatrilat for CNS diseases by considering its ability to penetrate the blood-brain barrier. The most potent stereoisomers against brain carboxylesterase were determined through molecular docking and homology modeling. Molecular dynamics simulation and structural analysis were performed to confirm the suitability of the prodrug structure for crossing the blood-brain barrier and binding to brain carboxylesterase. Additionally, the QM/MM calculation revealed the catalytic reaction mechanism of the prodrug against brain carboxylesterase.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Physical
Niko Prasetyo, Alberto Krishna Ksatria Winning Kusuma, La Ode Muhammad Iqbal
Summary: The spin component scale MP2/molecular mechanics molecular dynamics simulation was used to investigate the formation of hydration shell and dynamics of hydrated Cd2+ in a water environment. The first hydration shell consisted of six water molecules with an average distance of 2.27 Å between water and Cd2+. The dynamics were analyzed by calculating the mean residence time (MRT) of water molecules in the first and second hydration shells, which were determined to be 31.8 and 1.92 ps, respectively, indicating the strong influence of Cd2+ in the first shell. Despite the strong interaction between Cd2+ and water molecules in the first shell, the influence of ions in the second hydration shell remained weak.
INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Anna Rovaletti, Claudio Greco, Ulf Ryde
Summary: This study provides a new perspective on the hydrogenase activity of MoCu CO dehydrogenase by improving the in silico description of the enzyme. Energy refinement using the BigQM approach showed that improved van der Waals parameters can better describe the hydrogen-backbone interaction in the enzyme's active site, leading to enhanced binding modes of H-2.
JOURNAL OF MOLECULAR MODELING
(2021)
Article
Chemistry, Physical
Ramachandren Dushanan, Samantha Weerasinghe, Dhammike P. Dissanayake, Rajendram Senthilinithy
Summary: This study investigated the effect of HDAC inhibitors on the stability of the HDLP enzyme through various analyses, finding that LBH589 and PCI24781 are excellent candidates for further research as HDLP inhibitors.
MOLECULAR SIMULATION
(2022)
Article
Chemistry, Multidisciplinary
Jyoti Chauhan, Srinivas R. R. Maddi, Kshatresh Dutta Dubey, Subhabrata Sen
Summary: A novel inhibitor 8d was synthesized in this study, showing significant inhibition of Indoleamine-2,3-dioxygenase and tryptophan dioxygenases. The binding and conformational changes post-inhibitor binding were thoroughly studied through molecular docking, MD simulations, and QM/MM calculations, supporting its mechanism of inhibition and its importance in cancer research.
FRONTIERS IN CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Maureen Bilinga Tendwa, Lorna Chebon-Bore, Kevin Lobb, Thommas Mutemi Musyoka, Ozlem Tastan Bishop
Summary: The study aimed to derive AMBER force field parameters for Fe2+ centers in DPD enzyme to accurately describe the structure and function of the protein, particularly in relation to 5-FU drug efficacy and toxicity. The results provide crucial information for in silico cancer pharmacogenomics and drug discovery research, opening up new avenues for further studies in this field.
Review
Chemistry, Multidisciplinary
Taehwan Jang, Dooam Paik, Seung-Jae Shin, Hyungjun Kim
Summary: Solid-liquid interfaces play a crucial role in various scientific and technological systems. However, the research on interfacial structures is still limited due to the difficulties in experimental techniques. Computational methods provide a possible solution, but current molecular simulation methods have limitations in simulating large interfacial systems. In order to overcome these limitations, a mean-field quantum mechanics/molecular mechanics (QM/MM) method has been developed.
BULLETIN OF THE KOREAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Physical
Vanessa Nikolaiczyk, Jenny Irwan, Trang Nguyen, Joerg Fohrer, Philipp Elbers, Paul Schrank, Mehdi D. Davari, Andreas Kirschning
Summary: Computer-aided rational design was used to modify the substrate binding pocket of sesquiterpene synthase, resulting in the production of different sesquiterpene products. Amino acids W118 and F138 were found to play a strong role in controlling the stability and conformation of key intermediates.
CATALYSIS SCIENCE & TECHNOLOGY
(2023)
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
Plant Sciences
Yen T. H. Lam, Jana Hoppe, Quang N. Dang, Andrea Porzel, Alena Soboleva, Wolfgang Brandt, Robert Rennert, Hidayat Hussain, Mehdi D. Davari, Ludger Wessjohann, Norbert Arnold
Summary: Three new azepino-indole alkaloids, named purpurascenines A-C (1-3), along with a new-to-nature 7-hydroxytryptophan (4) and two known compounds, adenosine (5) and riboflavin (6), were isolated from the fruiting bodies of Cortinarius purpurascens. The structures of 1-3 were determined using spectroscopic analysis and ECD calculations. The biosynthesis of purpurascenine A (1) was investigated, and a biosynthetic route involving a direct Pictet-Spengler reaction between alpha-keto acids and 7-hydroxytryptophan (4) was proposed. Compound 1 showed no antiproliferative or cytotoxic effects against human cancer cells and exhibited some antagonistic effects on the 5-HT-dependent 5-HT2A activation and putative constitutive activity of the 5-HT2A receptor.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Biochemistry & Molecular Biology
Karen Rodriguez-Nunez, Alejandra Cortes-Monroy, Marcela Serey, Yunus Ensari, Mehdi D. Davari, Claudia Bernal, Ronny Martinez
Summary: This article investigates the effect of site saturation mutagenesis on Rhizobium sp. Histamine Dehydrogenase (Rsp HDH) and proposes a tradeoff between substrate affinity and substrate inhibition in the catalytic mechanism of HDHs, which provides new insights for enzyme engineering.
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
Biochemistry & Molecular Biology
Henry Struwe, Joern Droste, Dipendu Dhar, Mehdi D. Davari, Andreas Kirschning
Summary: A new FPP derivative with a shifted double bond has been discovered, which can be converted by sesquiterpene cyclases to form an unknown germacrene derivative. This finding sheds light on the cyclization mechanism of FPP.
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, Physical
Yiheng Liu, Zhongyu Li, Chenqi Cao, Xianzhi Zhang, Shuaiqi Meng, Mehdi D. Davari, Haijun Xu, Yu Ji, Ulrich Schwaneberg, Luo Liu
Summary: To overcome the complexity of protein sequence space, a study employed a machine learning approach combined with iterative generation and experimental data implementation, successfully identifying and validating multiple improved recombinant variants as well as comparing regression models. The research demonstrates the feasibility of integrating machine learning with experimental methods and proves effective in exploring potential variations within the protein sequence space.
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.