Article
Chemistry, Physical
Fabian Meyer, Raphael Frey, Mathieu Ligibel, Emine Sager, Kirsten Schroer, Radka Snajdrova, Rebecca Buller
Summary: In this study, directed evolution of the L-proline cis-4-hydroxylase SmP4H from Sinorhizobium meliloti resulted in significant improvements in the total turnover number, k(cat), and k(cat)/K-m of the hydroxylation reaction, leading to the desired gamma-hydroxylation product. Additionally, a single amino acid substitution in the active site allowed for the reprogramming of the enzyme to act predominantly as a desaturase, showcasing the potential of tyrosine to serve as a catalytic entity in the reaction mechanism. Investigation into substrate scope also revealed the acceptance of noncanonical amino acids by the engineered SmP4H variants.
Article
Chemistry, Physical
Lunjie Wu, Jianhong An, Xiaoran Jing, Chun-Chi Chen, Longhai Dai, Yan Xu, Weidong Liu, Rey-Ting Guo, Yao Nie
Summary: This study investigates the selectivity mechanism of L-Isoleucine dioxygenase (IDO) and improves its selectivity through mutation, providing a route for diversifying C-H hydroxylation-based active compounds.
Article
Chemistry, Applied
Erika Tassano, Charles Moore, Solene Dussauge, Alexandra Vargas, Radka Snajdrova
Summary: Genome mining was used to discover novel Fe(II)/alpha-ketoglutarate-dependent dioxygenases for expanding the enzymatic repertoire in the oxidation of L-proline. The study successfully predicted regio- and stereoselectivity in the hydroxylation reaction, validated the hypothesis experimentally, and isolated two novel byproducts in the reactions with enzymes from Bacillus cereus and Streptomyces sp. The research also investigated the mechanism for the formation of an epoxide through O-18-labeling experiment and demonstrated the synthetic potential of alpha KGDs on a preparative scale.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2022)
Article
Nutrition & Dietetics
Junquan Tian, Xuetai Bao, Fan Yang, Xiongzhuo Tang, Qian Jiang, Yuying Li, Kang Yao, Yulong Yin
Summary: Age-related osteoporosis is a common disease in the elderly, mainly caused by excessive activity of osteoclasts. Most approved drugs inhibit osteoclasts to treat osteoporosis. This study shows that supplementing dimethyl alpha-ketoglutarate (DM-AKG) can inhibit the differentiation of osteoclasts. The mechanism involves regulating NF-kappa B signaling pathway and oxidative phosphorylation through PHD1-dependent manner.
Article
Biochemistry & Molecular Biology
Rohan Jonnalagadda, Antonio Del Rio Flores, Wenlong Cai, Rimsha Mehmood, Maanasa Narayanamoorthy, Chaoxiang Ren, Jan Paulo T. Zaragoza, Heather J. Kulik, Wenjun Zhang, Catherine L. Drennan
Summary: The isonitrile moiety is essential in marine sponges and some microbes for various processes. Two biosynthetic routes have been identified, involving different sources of nitrogen and carbon atoms. Structural, biochemical, and computational investigations have shed light on the mechanism of isonitrile formation through an unprecedented reaction by the enzyme ScoE.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Zhi-Min Li, Ziwei Hu, Xiaoqin Wang, Suhang Chen, Weiyan Yu, Jianping Liu, Zhimin Li
Summary: In this study, the biochemical and structural properties of two α-ketoglutarate decarboxylases from cyanobacteria were investigated. It was found that the enzyme encoded by the MAE_06010 gene exhibited higher catalytic efficiency compared to the one encoded by the MiAbw_01735 gene. Further investigation revealed that MaKGD showed optimum activity at pH 6.5-7.0 and was most activated by Mg2+. The structural modeling and mutagenesis study provided insights into the binding pocket of MaKGD and the importance of certain residues in its catalysis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Wei Xu, Chirag H. Patel, Liang Zhao, Im-Hong Sun, Min-Hee Oh, Im-Meng Sun, Rachel S. Helms, Jiayu Wen, Jonathan D. Powell
Summary: GOT1 plays a crucial role in CD8+ T cell effector differentiation and function by maintaining redox balance and promoting purine nucleotide biosynthesis, glycolytic programming, and cytotoxic function, possibly through posttranslational regulation of HIF protein. Conversely, genetic deletion of GOT1 promotes the generation of memory CD8+ T cells.
Article
Chemistry, Physical
Qian Wei, Hai-Chun Zeng, Yi Zou
Summary: This study identified two parallel and complex pathways of fungal dioxafenestrane sesquiterpenes from terrestrial and marine-derived fungi, revealing their differences in late-stage tailoring steps. It also discovered important enzymes and catalytic steps, providing valuable insights for natural product generation and metabolic enzymes.
Article
Chemistry, Multidisciplinary
Christian A. Gomez, Dibyendu Mondal, Qian Du, Natalie Chan, Jared C. Lewis
Summary: Directed evolution was used to engineer variants of SadX, resulting in site-selective azidation and succinylation of amino acids and amines. This study provides a promising starting point for evolving SadX variants that can functionalize structurally distinct substrates and enable enzymatic C-H functionalization with non-native functional groups.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
Xuanzhong Liu, Zhenbo Yuan, Hao Su, Xiaodong Hou, Zhiwei Deng, Huibin Xu, Baodang Guo, Dejing Yin, Xiang Sheng, Yijian Rao
Summary: This study reveals the formation mechanism of the seven-membered methylenedioxy bridge in cercosporin biosynthesis, providing molecular insights into the biosynthetic pathways of natural products containing MDBs.
Article
Chemistry, Multidisciplinary
Hui Tao, Richiro Ushimaru, Takayoshi Awakawa, Takahiro Mori, Masanobu Uchiyama, Ikuro Abe
Summary: Non-heme iron enzymes are versatile catalysts in the biosynthesis of medicinal natural products and have practical applications in chemical synthesis. This study provides mechanistic insights into the atypical stereochemistry of the TqaL-catalyzed aziridination reaction, which involves both retention and inversion of the C3(C beta) stereocenter. Mutagenesis studies reveal the role of specific amino acid residues in regulating the reaction type and stereochemistry.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Food Science & Technology
Ewa Tomaszewska, Siemowit Muszynski, Anna Arczewska-Wlosek, Piotr Domaradzki, Renata Pyz-Lukasik, Janine Donaldson, Sylwester Swiatkiewicz
Summary: The study found that dietary supplementation of AKG did not significantly affect the cholesterol and total fat content of egg yolks, but resulted in both positive (reduced n-6 FA and increased MUFA) and negative (reduced PUFA and n-3 FA, increased TI and n-6/n-3 ratio) changes in the fatty acid profile.
Article
Endocrinology & Metabolism
Marie-Noelle Meaux, Jerome Harambat, Anya Rothenbuhler, Juliane Leger, Peter Kamenicky, Sylvie Soskin, Olivia Boyer, Emese Boros, Pascal D'Anella, Brigitte Mignot, Maite Gebhart, Philippe Vic, Nicolas Richard, Beatrice Thivichon-Prince, Bruno Francou, Agnes Linglart, Justine Bacchetta, Arnaud Molin
Summary: The study retrospectively collected clinical data of 24 cases of vitamin D-dependent rickets type 1A, and found that partial loss-of-function variation may be associated with a milder disease phenotype. Patients had good clinical, biochemical, and radiological outcomes after treatment, but adherence is crucial to prevent complications.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Jenna M. Greve, Andrew M. Pinkham, Zechariah Thompson, J. A. Cowan
Summary: HAAH is an important enzyme that binds both iron and calcium in its active site, with both metals playing different roles in enzyme stability and activity. Through experimental analysis, the importance of metal binding sites was discovered, along with the identification of a previously unreported residue crucial for HAAH catalysis.
Article
Biochemistry & Molecular Biology
Jun-Hong Kim, Huijin Cheon, Hye-Jin Jo, Ji-Won Kim, Ga Young Kim, Hye-Rim Seo, Pil-Won Seo, Jeong-Sun Kim, Jin-Byung Park
Summary: This study focuses on the engineering of C1 and C2 carboligases for the selective condensation of formaldehyde into erythrulose. By designing mutants and combining different variants, the catalytic activity and stability of the carboligases were significantly improved. This allowed for the efficient production of erythrulose from formaldehyde via glycolaldehyde, without the formation of byproducts.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Multidisciplinary
Page N. Daniels, Hyunji Lee, Rebecca A. Splain, Chi P. Ting, Lingyang Zhu, Xiling Zhao, Bradley S. Moore, Wilfred A. van der Donk
Summary: This study identified a new biosynthetic pathway in which glycyl-tRNA is used to attach amino acids to a ribosomally synthesized peptide, generating amino acid-derived natural products. This pathway involves multiple hydroxylations and chemical modifications.
Article
Biochemistry & Molecular Biology
Martin McLaughlin, Yue Yu, Wilfred A. van der Donk
Summary: This study investigates the role of the TglA scaffold in TglHI recognition and determines the specificity of TglHI towards the C-terminal residues of its substrate TglACys using in vitro transcription-coupled translation and expressed protein ligation. The results identify a synthetically accessible TglACys fragment sufficient for modification by TglHI and reveal the L-selenocysteine analog of TglACys, TglASec, as an inhibitor of TglHI.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Page N. Daniels, Wilfred A. van der Donk
Summary: The selective chemical or enzymatic functionalization of proteins is crucial for the preparation of protein conjugates. The tailoring enzyme BhaC1 has been found to convert tryptophan into a promising moiety for bioconjugation. This enzyme exhibits high selectivity and only tolerates minor changes to the peptide sequence.
Article
Chemistry, Multidisciplinary
Dinh T. Nguyen, Tung T. Le, Andrew J. Rice, Graham A. Hudson, Wilfred A. van der Donk, Douglas A. Mitchell
Summary: In this study, a method for enzymatic synthesis of pyridine-based macrocyclic peptides from linear precursor peptides is reported. It is demonstrated that the pyritide-forming enzymes recognize both the leader region and a C-terminal tripeptide motif, allowing for the generation of a wide range of pyritide analogues. This approach provides a broad substrate scope for the discovery and optimization of macrocyclic peptides.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Haoqian Liang, Isaiah J. Lopez, Marina Sanchez-Hidalgo, Olga Genilloud, Wilfred A. van der Donk
Summary: In this study, the in vitro biosynthesis process of class V lanthipeptide cacaoidin was reconstituted, and a novel dehydration enzyme CaoK and effector protein CaoY were discovered to play critical roles. Through mutagenesis studies and structure prediction, the importance of hydrophobic interactions in enzyme-substrate recognition was revealed.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Raymond Sarksian, Wilfred A. van der Donk
Summary: The three-dimensional structure of natural products is crucial for their biological activities, and enzymes have evolved to generate specific active stereoisomers. Lanthipeptides are post-translationally modified natural products with macrocyclic thioethers that have defined stereochemistry. This study compares two lanthipeptide biosynthetic gene clusters and reveals the importance of an additional enzyme domain in controlling product stereochemistry.
ACS CHEMICAL BIOLOGY
(2022)
Review
Chemistry, Multidisciplinary
Chayanid Ongpipattanakul, Emily K. Desormeaux, Adam DiCaprio, Wilfred A. van der Donk, Douglas A. Mitchell, Satish K. Nair
Summary: This review discusses the modes of action and interactions with natural targets of ribosomally synthesized and post-translationally modified peptides (RiPPs). The ease of engineering RiPPs provides potential opportunities for designing new or improved activities.
Article
Chemistry, Multidisciplinary
Satish K. Nair, Zeng-Fei Pei, Lingyang Zhu, Raymond Sarksian, Wilfred A. van der Donk
Summary: Lanthipeptides are cyclic peptides characterized by the presence of lanthionine or methyllanthionine thioether rings. Bioinformatics analysis identified over 240 lanthipeptide clusters. Reconstitution studies showed that the cyclase-catalyzed product is distinct from the spontaneous product. Structural characterization revealed that the cyclase diverts the final product to a different configuration. These studies highlight the importance of lanthipeptide cyclases in the biosynthesis of constrained peptides.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Raymond Sarksian, Lingyang Zhu, Wilfred A. van der Donk
Summary: This report demonstrates that the biosynthesis of lanthipeptides containing the d-allo-l-MeLan macrocycle proceeds through (E)-Dhb intermediates formed by net syn-elimination of l-Thr.
CHEMICAL COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Chayanid Ongpipattanakul, Shi Liu, Youran Luo, Satish K. Nair, Wilfred A. van der Donk
Summary: The addition of Cys to dehydroalanine (Dha) and dehy-drobutyrine (Dhb) in both eukarya and bacteria plays important roles in various biological processes. In bacteria, this addition is catalyzed by lanthipeptide cyclases (LanC) proteins to produce lanthipeptides. In eukarya, the addition of Cys in glutathione to Dha/Dhb is catalyzed by eukaryotic LanC-like (LanCL) enzymes to protect cellular proteome. The crystal structures of human LanCL1 enzyme complexed with different ligands reveal the mechanism of the enzyme-catalyzed thia-Michael addition involving zinc ion activation, protonation of enolate intermediate, and stabilization of negative charge.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Microbiology
Luke Bown, Ryuichi Hirota, Michelle N. Goettge, Jerry Cui, David T. Krist, Lingyang Zhu, Constantin Giurgiu, Wilfred A. van der Donk, Kou-San Ju, William W. Metcalf
Summary: The study reveals the biosynthetic pathway of phosphonothrixin, which can help design strains that overproduce this potentially useful herbicide.
JOURNAL OF BACTERIOLOGY
(2023)
Article
Chemistry, Organic
Nuria Mazo, Imran R. Rahman, Claudio D. Navo, Jesus M. Peregrina, Jesus H. Busto, Wilfred A. . van der Donk, Gonzalo Jimenez-Oses
Summary: This study reports a common strategy for the synthesis of lanthionine derivatives using nucleophilic ring opening of cyclic sulfamidates derived from amino acids. The researchers achieved regio-, chemo-, and stereoselective intramolecular S-alkylation of a cysteine residue with N-sulfonyl sulfamidates for the synthesis of cyclic lanthionine-containing peptides. Four different analogues of cytolysin S (CylLS '') were successfully synthesized and their conformational preferences and biological activities were compared with wild-type CylLS ''.
Article
Chemistry, Multidisciplinary
Richard S. Ayikpoe, Lingyang Zhu, Jeff Y. Chen, Chi P. Ting, Wilfred A. van der Donk
Summary: The domain of unknown function 692 (DUF692) is a family of enzymes involved in the biosynthesis of RiPP natural products. This study identified a new member of the DUF692 family, ChrH, and demonstrated its catalyzation of a unique chemical transformation. The characterization of ChrH expands the repertoire of reactions catalyzed by DUF692 enzymes.
ACS CENTRAL SCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Xuenan Mi, Emily K. Desormeaux, Tung T. Le, Wilfred A. van der Donk, Diwakar Shukla
Summary: This study investigated the influence of substrate sequence and solution structure on site-selectivity and order of ring formation in lanthipeptide biosynthesis. Molecular dynamic simulations revealed that the secondary structure of the core peptide played a crucial role in determining the final product's ring pattern. These findings contribute to our understanding of lanthipeptide biosynthesis and aid in bioengineering efforts for lanthipeptide-derived products.
Article
Chemistry, Multidisciplinary
Hyunji Lee, Chunyu Wu, Emily K. Desormeaux, Raymond Sarksian, Wilfred A. van der Donk
Summary: This study reports a new system for heterologous expression of class I lanthipeptides in Escherichia coli by co-expressing the producing organism's glutamyl-tRNA synthetase (GluRS) and tRNA(Glu) pair. The system allows for the production of fully-dehydrated peptides, including epilancin 15X and peptides from Bacteroidota Chryseobacterium and Runella strains. Additionally, LanCL enzymes were shown to remove glutathione adducts from C-glutathionylated peptides with dl or ll-lanthionine stereochemistry. These advancements will facilitate the discovery of new lanthipeptides through synthetic biology-driven genome mining efforts.
Review
Chemistry, Multidisciplinary
Dan He, Yawen Li, Fuwen Zhao, Yuze Lin
Summary: High trap density in organic solar cells leads to localized charge carriers and reduced carrier lifetime, limiting device efficiency. This feature article summarizes the recent advances of trap suppression by material design and device engineering.
CHEMICAL COMMUNICATIONS
(2024)
Review
Chemistry, Multidisciplinary
Olivier Monfort, Arshitha Madhusudhan, Martin Motola
Summary: This article presents the advantages of coupling photocatalysis and Fenton-based processes for environmental remediation and discusses their synergy. It critically examines the simultaneous triggering of these two processes and provides insights into research approaches. The study aims to enhance understanding of this complex process and highlight the potential integration of new catalysts in current wastewater treatment technology.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Manideepa Dhar, Chittaranjan Mishra, Avijit Das, Uttam Manna
Summary: An approach of 'polymerization of monomers in its aggregated form' has been introduced to tailor the water wettability of fibrous and porous substrates, achieving hydrophobicity to superhydrophobicity transition, as well as patterned wettability. This facile chemical method provides a durable coating with adjustable and patterned wettability for various potential applications.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Saswat Ranjan Bhoi, Chhanda Debnath, Shikha Gandhi
Summary: In this article, a novel catalytic reaction using Pd(0) and Bronsted acid is reported for the synthesis of biologically important imidazolidinone-fused N-heterocycles through redox-neutral intramolecular N-allylation of indoles and pyrroles with alkynes. This atom-economical method is applicable to a wide range of substrates and eliminates the need for leaving groups or oxidizing agents commonly used in traditional allylation reactions.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Longkun Chen, Mingshuai Zhang, Meichen Liu, Zhuoyuan Liu, Yuetong Qiu, Zhilai Zhang, Fuchao Yu, Jiuzhong Huang
Summary: In this study, an efficient Rh(III)-catalyzed selective mono- and dual-C-H bond functionalization/cyclization with iodonium ylide as the sole coupling partner was demonstrated. Fused benzodiazepine skeletons were obtained in excellent yields, providing an improved approach to dual C-H unsymmetrical functionalization.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Alice Kennett, Sven Epple, Gabriella van der Valk, Irene Georgiou, Evelyne Gout, Romain R. Vives, Angela J. Russell
Summary: This study presents the design and synthesis of sulfated disaccharide inhibitors based on IdoA(2S)-GlcNS(6S), which showed potent inhibition of Sulf-2. The results suggest that IdoA(2S)-GlcNS(6S) is the shortest fragment size required for effective inhibition of Sulfs, and a trisulfated disaccharide is identified as the minimal fragment size of heparan sulfate for effective endosulfatase inhibition.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Mauro Garbini, Andrea Brunetti, Riccardo Pedrazzani, Magda Monari, Massimo Marcaccio, Giulio Bertuzzi, Marco Bandini
Summary: The self-adaptability of galvanostatic electrolysis was found to be helpful in a multistage chemo- and diastereoselective electrochemically promoted cyclodimerization of chalcones. Through a series of reductive events, densely functionalized cyclopentanes with five contiguous stereocenters were obtained (25 examples, yields up to 95%, dr values up to >20:1). Further experimental and electrochemical investigations indicated the crucial role of dynamic kinetic resolution of the aldol intermediate in the reaction mechanism.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Dhananjay S. Nipate, Neha Meena, Prakash N. Swami, Krishnan Rangan, Anil Kumar
Summary: In this study, the synthesis of functionalized benzo[a]phenazines and indazolo[2,3-a]quinolines was achieved through Rh(III)-catalyzed oxidative annulation of 2-arylquinoxalines and 2-aryl-2H-indazoles with allyl alcohols. The method showed a wide substrate scope, excellent functional group tolerance, good to high yields of annulated products, and the capability for scaled-up synthesis. A tentative mechanism of the annulation reaction was proposed based on a preliminary mechanistic investigation.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Ruonan Zhang, Abudukadi Tudi, Xia Yang, Xuping Wang, Zhihua Yang, Shujuan Han, Shilie Pan
Summary: A new lead tellurium borate material with a unique fundamental building block [B4O10] was synthesized and found to exhibit high birefringence. The structure-property relationship was discussed using first-principles calculations.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Amresh Kumar Singh, Baishali Thakurta, Anupam Giri, Monalisa Pal
Summary: This study introduces three key concepts for the quick synthesis of large-scale high-quality 2D materials films and their utilization in device fabrication.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Reina Hagiwara, Shun Nishimura, Kosuke Okeyoshi
Summary: A copolymer-conjugated nanocatalytic system has been developed to improve electron transfer and enhance photoinduced H2 generation.
CHEMICAL COMMUNICATIONS
(2024)
