Article
Biochemical Research Methods
Sina A. Stierle, Lauritz Harken, Shu-Ming Li
Summary: Cyclodipeptides from fungi and bacteria, which are often modified by different tailoring enzymes, have various biological and pharmacological activities. In this study, we used genetic engineering to design modified cyclodipeptides by incorporating gtmA core gene and gtmB-gtmE genes from the silent guatrypmethine gene cluster of Streptomyces cinnamoneus. Addition of different cyclodipeptides to the transformant led to the detection of diverse pathway products. Coexpression of CDPS genes from multiple Streptomyces strains with gtmB-gtmE resulted in the formation of diketopiperazine derivatives with varying modification stages. Our results demonstrate the potential of rational gene combination to increase structural diversity.
ACS SYNTHETIC BIOLOGY
(2023)
Review
Biotechnology & Applied Microbiology
Lauritz Harken, Shu-Ming Li
Summary: 2,5-Diketopiperazines are the smallest cyclic peptides composed of two amino acids connected by two peptide bonds, which can be biosynthesized by different enzyme families in nature. Due to their stable scaffold, they can serve as precursors for various tailoring enzymes to generate intriguing secondary metabolites. Recent attention has been focused on cyclodipeptide synthase-associated P(450)s, as they can catalyze a wider range of reactions beyond oxidation.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Martin Grininger
Summary: Modular polyketide synthases (PKSs) are highly organized enzymes that run catalytic reactions over multiple steps. These enzymes form complex multienzyme complexes and produce complex polyketide products. Recent structural insights have provided valuable information about the orchestration of catalytic events within PKSs, leading to new possibilities in PKS engineering.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Munro Passmore, Angelo Gallo, Jozef R. Lewandowski, Matthew Jenner
Summary: This study reveals specific interactions between ACP and KR domains from trans-AT PKSs, indicating highly optimized interaction interfaces driven by evolutionary processes. The results provide valuable rules for future engineering efforts of biosynthetic assembly lines.
Article
Plant Sciences
Jing Liu, Yiling Yang, Xiulan Xie, Shu-Ming Li
Summary: Heterologous expression of a cdps-p450 locus from Streptomyces sp. NRRL S-1521 led to the identification of a new guaninylated diketopiperazine, guanitrypmycin D1. The cytochrome P450 GutD1521 catalyzes the regiospecific transfer of guanine to C-2 of the indole ring of cyclo-(L-Trp-L-Tyr) via a C-C linkage, representing a new chemical transformation within this enzyme class. Furthermore, GutD1521 efficiently accepts several other tryptophan-containing cyclodipeptides or derivatives for regiospecific coupling with guanine, thus generating different guanitrypmycin analogs.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Biochemistry & Molecular Biology
Anastasia Croitoru, Morgan Babin, Hannu Myllykallio, Muriel Gondry, Alexey Aleksandrov
Summary: The study investigates the interaction between CDPS and tRNA substrate using AlbC as a model, revealing significant contributions of AlbC alpha-helix residues to tRNA binding. The simulation results explain the biochemical data well and suggest that tRNAs of the first and second substrates interact with AlbC in a similar manner. The mechanism of protein:tRNA interaction is expected to be relevant to a wide range of proteins based on the high degree of sequence and structural similarity among CDPS NYH protein subfamily members.
Review
Biochemistry & Molecular Biology
Sarah Bonhomme, Andrea Dessen, Pauline Macheboeuf
Summary: NRPSs are multienzymes that produce complex natural metabolites with applications in medicine and agriculture. They consist of multiple catalytic domains and non-catalytic carrier protein domains, allowing flexibility in catalyzing and transporting products. Recent studies providing structural views of multi-domain NRPSs have enhanced understanding of their catalytic cycle.
Article
Chemistry, Multidisciplinary
Bing Jiang, Marcos Gil-Sepulcre, Pablo Garrido-Barros, Carolina Gimbert-Surinach, Jia-Wei Wang, Jordi Garcia-Anton, Pau Nolis, Jordi Benet-Buchholz, Nuria Romero, Xavier Sala, Antoni Llobet
Summary: A cobalt complex with a kappa-N3P2 ligand is stable in air and exhibits good electrochemical behavior. It can catalyze the hydrogen evolution reaction and be regenerated with the addition of CoCp*(2).
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Rosiane Andrade da Costa, Isadora Emanoela Pereira Costa Andrade, Otavio Henrique Bezerra Pinto, Beatriz Blenda Pinheiro de Souza, Debora Luiza Albano Fulgencio, Marise Leite Mendonca, Adriane Silva Kurokawa, Daniel Barros Ortega, Lucas Silva Carvalho, Ricardo Henrique Kruger, Marcelo Henrique Soller Ramada, Cristine Chaves Barreto
Summary: A study identified a novel variant of antimicrobial peptides, tridecaptin G1 and G2, produced by Paenibacillus elgii AC13. These variants exhibited antimicrobial activity against various bacteria and fungi.
Article
Biochemistry & Molecular Biology
Christian Hobson, Matthew Jenner, Xinyun Jian, Daniel Griffiths, Douglas M. Roberts, Matias Rey-Carrizo, Gregory L. Challis
Summary: This study reports the discovery of a new variant of a dehydratase domain that eliminates two molecules of water in sequential steps during polyketide chain assembly, leading to the introduction of a conjugated E,Z-diene. These findings expand the catalytic versatility of modular PKSs and highlight the role of a conserved histidine residue in the reaction.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Peng Wu, Yang Gu, Langxing Liao, Yanfei Wu, Jiaoyu Jin, Zhanfeng Wang, Jiahai Zhou, Sason Shaik, Binju Wang
Summary: A coordination switch of the sulfoxide intermediate is involved in the catalysis of non-heme iron EgtB, driven by S/pi electrostatic interactions, which efficiently promotes selective C-S bond formation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biotechnology & Applied Microbiology
Wen Li, Lindsay Coby, Jing Zhou, Shu-Ming Li
Summary: Ascomycetous fungi can produce both harmful mycotoxins and valuable drug candidates. This study demonstrates the ability to increase structural diversity by reprogramming natural biosynthetic pathways and also discovers a previously unknown catalytic reaction of an enzyme.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Infectious Diseases
Benjamin Youenou, Patricia Martins Simoes, Anne Tristan, Eric Farfour, Clemence Beauruelle, Camille Kolenda, Anne-Gaelle Ranc, Francois Vandenesch, Frederic Laurent, Celine Dupieux
Summary: This study describes the presence of linezolid-resistant MRSA strains carrying the cfr(B) gene in the French National Reference Centre for staphylococci. The strains showed resistance to linezolid but susceptibility to tedizolid, and carried the cfr(B) gene on the same chromosomal transposon. This finding highlights the risk of horizontal transfer of oxazolidinone resistance genes in Staphylococcus aureus.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Songya Zhang, Lin Zhang, Anja Greule, Julien Tailhades, Edward Marschall, Panward Prasongpholchai, Daniel J. Leng, Jingfan Zhang, Jing Zhu, Joe A. Kaczmarski, Ralf B. Schittenhelm, Oliver Einsle, Colin J. Jackson, Fabrizio Alberti, Andreas Bechthold, Youming Zhang, Manuela Tosin, Tong Si, Max J. Cryle
Summary: WS9326A is a peptide antibiotic synthesized by a non-ribosomal peptide synthetase (NRPS). The cytochrome P450 encoded by sas16 (P450Sas) is critical for the formation of an unusual amino acid residue in WS9326A. In this study, the researchers identified the substrate of P450Sas and elucidated its role in the biosynthetic pathway of WS9326A. The results suggest that P450Sas catalyzes the direct dehydrogenation of a dipeptide intermediate, expanding the range of P450 enzymes that can be used for the production of biologically active peptides.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Biochemistry & Molecular Biology
Dongqi Yi, Dhirendra Niroula, Will R. Gutekunst, Joyce E. Loper, Qing Yan, Vinayak Agarwal
Summary: By conducting in vitro enzymatic production, researchers discovered that a specific type of bacterial polyketide synthase does not produce aromatic products, but instead produces an alicyclic dihydrophloroglucinol which is later enzymatically dehydrated and aromatized. The presence of the aromatizing dehydratase in the pyoluteorin biosynthetic gene cluster is critical for the antibiotic activity of pyoluteorin.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anastasia Croitoru, Morgan Babin, Hannu Myllykallio, Muriel Gondry, Alexey Aleksandrov
Summary: The study investigates the interaction between CDPS and tRNA substrate using AlbC as a model, revealing significant contributions of AlbC alpha-helix residues to tRNA binding. The simulation results explain the biochemical data well and suggest that tRNAs of the first and second substrates interact with AlbC in a similar manner. The mechanism of protein:tRNA interaction is expected to be relevant to a wide range of proteins based on the high degree of sequence and structural similarity among CDPS NYH protein subfamily members.
Article
Neurosciences
Miguel Salinas, Pascal Kessler, Dominique Douguet, Daad Sarraf, Nicolo Tonali, Robert Thai, Denis Servent, Eric Lingueglia
Summary: This study elucidated the inhibition mechanism of the snake venom toxin Mamb-1 on the acid-sensing ion channel ASIC1a through structure-activity relationship, molecular dynamics simulation, and experimental research. It provides important insights for further improvement and optimization of ASIC blockers.
Article
Biochemistry & Molecular Biology
Poulomi Das, Khac Huy Ngo, Fernaldo Richtia Winnerdy, Arijit Maity, Blaz Bakalar, Yves Mechulam, Emmanuelle Schmitt, Anh Tuan Phan
Summary: This study investigates the adaptability of left-handed G4 structures towards the presence of bulges, presenting the structural characteristics of left-handed G4s accommodating varying numbers of bulges. Bulges in left-handed G4s exhibit distinct features compared to those in right-handed G4s, and elucidation of the intricate structural details may enhance understanding of the potential roles and limitations of these unique structures.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Monika Kaminska, Pierrick Bruyat, Carole Malgorn, Marion Doladilhe, Evelyne Cassar-Lajeunesse, Carole Fruchart Gaillard, Melissa De Souza, Fabrice Beau, Robert Thai, Isabelle Correia, Andrzej Galat, Dimitris Georgiadis, Olivier Lequin, Vincent Dive, Sarah Bregant, Laurent Devel
Summary: Activity-based probes can discriminate active enzymes from inactive counterparts, targeting metalloproteases through reversible inhibitors with photo-crosslinkers. Novel probes were developed to covalently modify active matrix metalloproteases without external trigger, allowing for nanogram-scale reactions with recombinant MMPs in complex proteomes. This ligand-directed chemistry successfully labeled active MMP-12 secreted by eukaryote cells, with potential applications for other metalloproteases in unresolved proteomic profiling in vivo.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Environmental Sciences
Denis Servent, Carole Malgorn, Mylene Bernes, Sophie Gil, Christelle Simasotchi, Anne-Sophie Herard, Thierry Delzescaux, Robert Thai, Peggy Barbe, Mathilde Keck, Fabrice Beau, Armen Zakarian, Vincent Dive, Jordi Molgo
Summary: Pinnatoxins (PnTx) are an emerging phycotoxin family, widely distributed in contaminated shellfish, known for their high toxicity and ability to rapidly cross physiological barriers. Studies have shown that PnTx-G can be rapidly cleared from the body, accumulate in the liver and small intestine, and exhibit selective binding to muscle and neuronal nAChR subtypes.
SCIENCE OF THE TOTAL ENVIRONMENT
(2021)
Article
Multidisciplinary Sciences
Yuanyuan Liao, Yves Mechulam, Benedikt Lassalle-Kaiser
Summary: This study presents a novel microfluidic mixer based on the staggered herring bone pattern and split-recombination strategies, which improves mixing efficiency and reduces sample consumption. The optimized geometry allows for controlled flow structure rotation and increased contact surface, leading to enhanced mixing effects. The device, fabricated using soft-lithography, demonstrates good mixing performance under low flow rate and small working volume conditions, making it suitable for studies with precious samples.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Medicinal
Heloise Cahuzac, Antoine Sallustrau, Carole Malgorn, Fabrice Beau, Peggy Barbe, Victor Babin, Steven Dubois, Alberto Palazzolo, Robert Thai, Isabelle Correia, Ki Baek Lee, Sebastien Garcia-Argote, Olivier Lequin, Mathilde Keck, Herve Nozach, Sophie Feuillastre, Xin Ge, Gregory Pieters, Davide Audisio, Laurent Devel
Summary: This article presents a bioanalytical strategy based on dual radiolabeling and ex vivo digital imaging for accurate determination of the plasma and tissue profiles of protein-drug conjugates. The strategy involves enzymatic and chemical reactions to obtain dual-labeled anti-MMP-14 Fabs conjugated to monomethyl auristatin E, allowing for simultaneous monitoring and accurate quantification of the components during circulation phase and accumulation in different organs.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Ramy Kazan, Gabrielle Bourgeois, Christine Lazennec-Schurdevin, Eric Larquet, Yves Mechulam, Pierre-Damien Coureux, Emmanuelle Schmitt
Summary: This study investigates the late steps of translation initiation in Pyrococcus abyssi and reveals that aIF5B bound to GTP accelerates subunit joining without GTP hydrolysis. Crystal structures and cryo-EM analysis demonstrate the cooperative role of archaeal 5B and 1A factors in promoting a conformation of the initiator tRNA favorable to subunit joining.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemical Research Methods
Frank Gabel, Sylvain Engilberge, Emmanuelle Schmitt, Aurelien Thureau, Yves Mechulam, Javier Perez, Eric Girard
Summary: Small-angle X-ray scattering (SAXS) is an important tool in structural biology, providing information about the structure and interactions of biomolecules. However, the application of contrast-variation SAXS is limited by the range of solvent electron densities and the destabilizing effect of some co-solutes on biological systems.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ramy Kazan, Gabrielle Bourgeois, Dominique Carisetti, Ileana Florea, Eric Larquet, Jean-Luc Maurice, Yves Mechulam, Francois Ozanam, Emmanuelle Schmitt, Pierre-Damien Coureux
Summary: Sample preparation on cryo-EM grids is crucial and can lead to varying results. By employing multiple techniques to investigate the characteristics of the grids, we were able to diagnose and address grid preparation issues, ultimately adjusting the preparation parameters.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Cristina Cardenal Peralta, Paul Vandroux, Lea Neumann-Arnold, Michel Panvert, Jerome Fagart, Wolfgang Seufert, Yves Mechulam, Emmanuelle Schmitt
Summary: Eukaryotic initiation factor 2 (eIF2) plays a key role in protein synthesis and regulation. Cdc123 facilitates the assembly of eIF2 and binds to its γ subunit. Mutations related to MEHMO syndrome affect Cdc123-mediated eIF2 assembly. The crystallographic structure of Cdc123 bound to the γ domain of eIF2 was determined.
JOURNAL OF STRUCTURAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Vaitea Opuu, Giuliano Nigro, Christine Lazennec-Schurdevin, Yves Mechulam, Emmanuelle Schmitt, Thomas Simonson
Summary: Amino acids with noncanonical backbones are important for protein engineering, but optimizing their properties is challenging. In this study, a computational protein design method was used to redesign an aminoacyl-tRNA synthetase and improve its activity towards noncanonical amino acids.
Article
Chemistry, Multidisciplinary
Poulomi Das, Fernaldo Richtia Winnerdy, Arijit Maity, Yves Mechulam, Anh Tuan Phan
Summary: A recent study identified a new motif involved in the formation of left-handed G-quadruplex DNA and determined the X-ray crystal structure of an LHG4 containing this motif. Structural analysis revealed the importance of split guanines and single thymine loops in promoting LHG4 formation.
CHEMICAL COMMUNICATIONS
(2021)
