Article
Chemistry, Multidisciplinary
Jie Fan, Huomiao Ran, Peng-Lin Wei, Yuanyuan Li, Huan Liu, Shu-Ming Li, Youcai Hu, Wen-Bing Yin
Summary: The biosynthetic pathway of pretrichodermamide A (1) in Trichoderma hypoxylon involves multiple enzymes that generate diverse fungal epidithiodiketopiperazines (ETPs). The study identified seven tailoring enzymes encoded by the tda cluster, including P450s TdaB and TdaQ for 1,2-oxazine formation, TdaI for C7'-hydroxylation, TdaG for C4, C5-epoxidation, methyltransferases TdaH for C6'- and TdaO for C7'-O-methylation, and reductase TdaD for furan opening. Deletion of genes led to the discovery of 25 novel ETPs, indicating the catalytic promiscuity of Tda enzymes. This research uncovers a hidden library of ETP alkaloids and enhances our understanding of the chemical diversity of natural products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Hao-Yu Jia, Zi-Yue Yang, Qi Chen, Min-Hua Zong, Ning Li
Summary: This study improved the promiscuous alcohol dehydrogenase activity of reductive aminase from Aspergillus oryzae through site-directed mutagenesis, with variant N93A showing enhanced catalytic efficiency. Key amino acid residues were identified for mutation by molecular docking, and the introduction of variant N93A resulted in improved substrate conversions and selectivities in Escherichia coli cells.
FRONTIERS IN CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
David Kreutter, Philippe Schwaller, Jean-Louis Reymond
Summary: Training a molecular transformer model with multi-task transfer learning and combining extensive reaction and enzymatic transformation data allows for accurate prediction of the structure and stereochemistry of enzyme-catalyzed reaction products.
Article
Chemistry, Physical
Jian Yang, Yunzhu Xiao, Yu Liu, Ru Li, Lijuan Long
Summary: The recruitment and rapid evolution of promiscuous catalysis led to a new efficient biocatalyst for organophosphrus remediation, with a 10,000-fold increase in methyl-parathion hydrolysis and broadened substrate specificity. Structural, kinetic, and computational comparisons identified the molecular basis for the enhanced catalysis and revealed how the mutations reshaped the substrate pocket for better access to catalytic machinery.
CATALYSIS SCIENCE & TECHNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xiaotong Wang, Zongjie Wang, Zhiqi Dong, Yihai Yan, Youming Zhang, Liujie Huo
Summary: In this study, three novel lanthipeptides pseudorosin A-C were characterized by heterologous expression of a class I lanthipeptide biosynthetic gene cluster from marine Pseudoalteromonas flavipulchra S16. It was found that the dehydratase PsfB could catalyze the dethiolation of specific Cys residues in all three core peptides, generating dehydroalanines in the absence of LanC cyclase. This is the first report of a member of the LanB dehydratase family performing glutamylation and subsequent elimination on Cys thiol groups.
ACS CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Chen Zhuo, Chengwei Zeng, Rui Yang, Haoquan Liu, Yunjie Zhao
Summary: RNA plays important roles in various biological processes and its conformational dynamics are crucial for carrying out diverse functions. In this study, a computational approach called RPflex was proposed to analyze pocket flexibility using a coarse-grained network model. The results showed strong correlations between flexibility scores and root-mean-square fluctuation values, and long-range interaction changes contributed most to flexibility. The computational analysis of pocket flexibility could be useful for RNA engineering in biological or medical applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Analytical
Julius Fuersch, Carsten Voormann, Kai-Michael Kammer, Florian Stengel
Summary: Small heat-shock proteins (sHSPs) play important roles in the cellular stress response across all species, primarily by binding early unfolding states of proteins to prevent aggregation. Research on yeast Hsp26 using cross-linking mass spectrometry (XL-MS) has provided detailed structural information on sHSP activation and client binding, revealing the significance of the middle domain in client-independent interaction and potential client specificity through additional binding sites within its alpha-crystallin domain and C-terminal extension.
ANALYTICAL CHEMISTRY
(2021)
Article
Biochemical Research Methods
Steven R. LaPlante, Valerie Roux, Fatma Shahout, Gabriela LaPlante, Simon Woo, Maria M. Denk, Sacha T. Larda, Yann Ayotte
Summary: This research protocol focuses on monitoring the solution behavior of drugs using NMR to reveal nano-entities formed due to self-associations. By employing various NMR techniques and other characterization methods, the properties of drugs in solution can be evaluated within days for compounds in a library.
Article
Chemistry, Organic
Yuanyuan Xu, Dan Li, Guishan Tan, Yan Zhang, Zhansheng Li, Kangping Xu, Shu-Ming Li, Xia Yu
Summary: In this study, successful prenylation or geranylation of biflavonoids using fungal prenyltransferase CdpC3PT and its mutants was reported. F253 was identified as a key residue related to donor selectivity, enabling the precise switching from utilizing DMAPP to GPP at the same C-3''' site of biflavonoids. Furthermore, residue W181 was discovered to generally increase prenylation activity towards biflavonoids.
Article
Chemistry, Physical
Max Linhorst, Jasper Wattjes, Bruno M. Moerschbacher
Summary: Chitosans, derived from chitin, are versatile biopolymers with unique properties that can be further improved through biocatalytic N-acylation. Using recombinant chitin deacetylase for N-acylation can yield highly substituted chitosan polymers, which can be further functionalized using copper-catalyzed reactions. This chemoenzymatic approach offers a pathway to a wide variety of functionalized chitosans with nonrandom substitution patterns.
Article
Biochemistry & Molecular Biology
Lorela Paco, John C. Hackett, William M. Atkins
Summary: Cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of various drugs and toxins. The interactions between CYP3A4 and ligands are difficult to predict due to its promiscuity and conformational flexibility. Through the use of hydrogen deuterium exchange mass spectrometry (HDX-MS), we investigated the effect of ligands on nanodisc-embedded CYP3A4, and found that ligands have differential effects on the flexibility of different regions of the enzyme. Molecular dynamics simulations showed that ligands can modulate long-range interactions and propagate local backbone fluctuations from the binding site to flexible regions of CYP3A4. Contrary to the common paradigm, a wide range of ligands actually increase the overall dynamics of CYP3A4, including regions remote from the active site.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Wei Dai, Ang Li, Nathan J. Yu, Thao Nguyen, Robert W. Leach, Martin Wuhr, Ralph E. Kleiner
Summary: The study utilized RNABPP strategy to investigate RNA-modifying enzyme activity in human cells, revealing mechanisms of m(5)C and m(5)U methyltransferases and a novel crosslink between 5-FUrd-modified RNA and DUS3L. The findings showed that DUS3L-knockout (KO) cells exhibited compromised protein translation rates and impaired cellular proliferation, indicating a potential role of DUS3L in epitranscriptomic RNA regulation.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Jessica E. Besaw, Jorg Reichenwallner, Paolo De Guzman, Andrejs Tucs, Anling Kuo, Takefumi Morizumi, Koji Tsuda, Adnan Sljoka, R. J. Dwayne Miller, Oliver P. Ernst
Summary: In this study, the crystal structure of Thermoplasmatales archaeon SG8-52-1 heliorhodopsin (TaHeR) was determined under low pH conditions. The structure revealed the accommodation of a chloride anion in the hydrophilic Schiff base cavity (SBC), stabilizing the protonated retinal Schiff base. Computational studies further supported an intramolecular signaling transduction pathway, with allosteric network changes propagating from the perturbed SBC to the intracellular and extracellular space. These findings suggest the potential sensory role of TaHeR as a rhodopsin.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Multidisciplinary
Gorjan Stojanovski, Helen C. Hailes, John M. Ward
Summary: This study presents a chemoenzymatic approach for regioselective modification of aminoglycoside antibiotics. The method allows for facile synthesis of novel compounds with potential antimicrobial activity against drug-resistant pathogens.
Article
Chemistry, Physical
Bernd A. Nebel, Michael Breuer, Andreas Schneider, Benjamin Aberle, Stephan C. Hammer, Per-Olof Syren, Martin J. Weissenborn, Bettina M. Nestl
Summary: This article reflects on Professor Bernhard Hauer's distinguished career in biocatalysis and highlights his contributions to the application and development of enzymes.
Article
Biochemical Research Methods
Nicolas A. Pabon, Yan Xia, Samuel K. Estabrooks, Zhaofeng Ye, Amanda K. Herbrand, Evelyn Suss, Ricardo M. Biondi, Victoria A. Assimon, Jason E. Gestwicki, Jeffrey L. Brodsky, Carlos J. Camacho, Ziv Bar-Joseph
PLOS COMPUTATIONAL BIOLOGY
(2018)
Article
Cell Biology
Mikhail S. Chesnokov, Marianna Halasi, Soheila Borhani, Zarema Arbieva, Binal N. Shah, Rick Oerlemans, Irum Khan, Carlos J. Camacho, Andrei L. Gartel
Summary: STL427944 selectively suppresses FOXM1 by inducing its relocalization and subsequent degradation, leading to increased sensitivity of cancer cells to conventional chemotherapeutic treatments.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
R. A. Degiosio, P. G. Needham, O. A. Andrews, H. Tristan, M. J. Grubisha, J. L. Brodsky, C. Camacho, R. A. Sweet
Summary: MAP2 phosphorylation plays a critical role in regulating cytoskeletal functions in neurons. Recent research has shown that phosphorylation of MAP2 in the proline-rich and C-terminal domains of the protein affects cellular functions including microtubule assembly, microtubule binding, actin binding, and actin polymerization.