Article
Chemistry, Physical
Michael J. Martinez, Jessica D. Carder, Evan L. Taylor, Eric P. Jacobo, ChulHee Kang, J. A. Brozik
Summary: This study measured the thermodynamic driving forces responsible for how strongly CPR partitions into a biomimetic ER with the same lipid composition. Results showed that the redox states of CPR have a significant impact on these driving forces.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Oncology
Hong Jiacong, Yang Qirui, Li Haonan, Song Yichang, Chen Yan, Chen Keng
Summary: Osteosarcoma is the most common primary bone cancer in adolescents with a poor prognosis. Current treatments are not satisfactory, therefore, it is critical to develop novel therapeutic strategies. This study discovered that zoledronic acid (ZOL) induces ferroptosis by upregulating POR expression in osteosarcoma cells. Knockdown of POR attenuated ZOL-induced cytotoxicity and the effect of ferroptosis. ZOL also inhibits osteosarcoma growth in vivo. These findings suggest that POR could be used as a therapeutic target to inhibit osteosarcoma.
Article
Plant Sciences
Pramesti Istiandari, Shuhei Yasumoto, Pisanee Srisawat, Keita Tamura, Ayaka Chikugo, Hideyuki Suzuki, Hikaru Seki, Ery Odette Fukushima, Toshiya Muranaka
Summary: Research reveals that different plant CPR classes have varied effects on triterpenoid production when co-expressed with different CYP classes. Co-expression of these genes in yeast can lead to higher yields and more valuable compounds.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Multidisciplinary Sciences
Philippe Urban, Denis Pompon
Summary: Conformational dynamics is crucial for the function of multidomain electron transfer complexes. Cryo-electron microscopy provides more information on dynamics compared to crystallographic or NMR approaches. AlphaFold has successfully predicted protein complexes, but its ability to address large conformational changes involved in catalysis has been unclear. In this study, a competitive modelling approach (CMA) was used to assess alternate conformations of the bacterial CYP102A1 monooxygenase homodimer. The predictions were compared to crystallographic and cryo-EM data, showing consistencies and allowing reinterpretation of experimental data.
SCIENTIFIC REPORTS
(2022)
Article
Food Science & Technology
Asja Ceranic, Thomas Svoboda, Franz Berthiller, Michael Sulyok, Jonathan Matthew Samson, Ulrich Gueldener, Rainer Schuhmacher, Gerhard Adam
Summary: This study identified and characterized the genes encoding fusaproliferin biosynthetic enzymes in Fusarium proliferatum, showing the significant roles of specific enzymes for fusaproliferin production. The knock-out mutants further confirmed the functions of these enzymes and provided insights into the biosynthesis of fusaproliferin and its novel derivatives.
Article
Biochemistry & Molecular Biology
Lingli Chen, Mei Tian, Baolong Jin, Biwei Yin, Tong Chen, Juan Guo, Jinfu Tang, Guanghong Cui, Luqi Huang
Summary: This study combines metabolomics and transcriptomics to unveil the biosynthesis pathway of Diterpene alkaloids (DAs) in Aconitum. It provides a rich dataset of full-length transcriptomes, systemic metabolomes, and gene expression profiles, setting the groundwork for further investigation of the biosynthesis pathway of C-20-DAs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Electrochemistry
Celia M. Silveira, Patricia R. Rodrigues, Wissam Ghach, Sofia A. Pereira, Francisco Esteves, Michel Kranendonk, Mathieu Etienne, M. Gabriela Almeida
Summary: The study investigated the direct electrochemical response of membrane-bound human cytochrome P450 1A2 on pyrolytic graphite electrodes encapsulated in a sol-gel matrix. It showed that CYP1A2 is highly sensitive to O-2 and easily inactivated under aerobic conditions, but remains active when in the presence of its electron donor partner, cytochrome P450 oxidoreductase (CPR). This highlights the crucial role of CPR in stabilizing the immobilized CYP1A2 enzyme and preserving O-2 electrocatalysis in this electrochemical set-up.
Article
Plant Sciences
Pramesti Istiandari, Shuhei Yasumoto, Hikaru Seki, Ery Odette Fukushima, Toshiya Muranaka
Summary: This study reveals that CPR classes I and II play different roles in triterpenoid biosynthesis in L. japonicus, with CPR class I potentially playing a crucial role in plant basal metabolism.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Yuan Gao, Jingjing Ma
Summary: This study found that the A503V polymorphism can affect the metabolism of tacrolimus catalyzed by CYP3A5, and may serve as a potential biomarker for tacrolimus treatment in transplantation recipients.
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yvonne Carius, Michael Hutter, Flora Kiss, Rita Bernhardt, C. Roy D. Lancaster
Summary: This study revealed the crystal structure of cytochrome P450 CYP106A1 from Priestia megaterium, which shows a rare sixth beta-sheet. Comparison with the previously studied CYP106A2 and docking studies with the substrate cortisol revealed a different orientation of the steroid molecule in the active sites, explaining the observed differences in substrate conversion and product formation by the two enzymes.
Article
Biochemistry & Molecular Biology
Qiuling Tang, Xuchao Li, Yanping He, Kangsheng Ma
Summary: The study reveals the significant role of the CPR gene in insecticide resistance in Aphis gossypii. The expression of AgCPR is influenced by the developmental stage and concentration of insecticide, and silencing of AgCPR increases susceptibility to the insecticide, indicating its functional importance.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yana Y. Toporkova, Elena O. Smirnova, Natalia V. Lantsova, Lucia S. Mukhtarova, Alexander N. Grechkin
Summary: The CYP74 clan enzymes play a crucial role in oxidative metabolism of polyunsaturated fatty acids in various organisms. A novel CYP440A18 enzyme from the Asian lancelet was characterized with dual EAS/AOS activity, being the first CYP74 clan enzyme of Chordata species possessing AOS activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Vladimir Mishin, Diane E. Heck, Yi-Hua Jan, Jason R. Richardson, Jeffrey D. Laskin
Summary: A characteristic of cytochrome P450 (CYP) enzymes is their ability to produce H2O2, which can lead to cellular oxidative stress and tissue damage. This study aimed to determine if specific form inhibitors could differentiate between the monooxygenase and NADPH oxidase activities of CYP enzymes. The findings suggest that form-specific inhibitors can effectively distinguish these two activities.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yichao Zhang, Hongli Li, Shaohang Yuan, Haihua Wu, Xiaojian Liu, Jianzhen Zhang
Summary: This study found that NADPH-cytochrome P450 reductase (CPR) in Locusta migratoria is involved in the activation of Precocene I. Experimental results showed that LmCPR interacts with NADPH, FAD, and FMN through hydrogen bonds. Treatment with Precocene I reduced the juvenile hormone levels in nymphs and prolonged the interval between fourth and fifth instar nymphs. Knockdown of LmCPR gene weakened the response to Precocene I, leading to a decrease in the occurrence rate of precocious adults induced by Precocene I treatment.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Paul A. Hubbard, Chuanwu Xia, Anna L. Shen, Jung-Ja P. Kim
Summary: The influence of the carboxy-terminal residues of NADPH-cytochrome P450 oxidoreductase (CYPOR) on catalytic activity and structure has been investigated, showing that deletion of bulky residues at the carboxy terminus can lead to increased mobility and altered interactions with cofactors. Moreover, deletion or substitution of Trp677 combined with deletion of Ser678 can result in changes in the enzyme's affinity for NADP+ and alterations in cytochrome c reductase activity.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Plant Sciences
Cecilie Cetti Hansen, Mette Sorensen, Matteo Bellucci, Wolfgang Brandt, Carl Erik Olsen, Jason Q. D. Goodger, Ian E. E. Woodrow, Birger Lindberg Moller, Elizabeth H. J. Neilson
Summary: This study investigates the biosynthesis of prunasin, a cyanogenic glucoside, in the economically and ecologically important genus Eucalyptus. By comparing cyanogenic and acyanogenic species, researchers identified a novel UDP-glucosyltransferase UGT87 that catalyzes the final step of prunasin biosynthesis. Additionally, the loss of different ortholog prunasin biosynthetic genes was observed in acyanogenic species. These findings highlight the heterogeneity and dynamic evolution of chemical defense pathways within a single genus, providing insights into the adaptability of Eucalyptus trees.
Article
Biochemistry & Molecular Biology
Line Fentz Rasmussen, Jennifer Anton, Louise Kjaerulff, Yong Zhao, Susan J. Semple, Ndi Chi, Bevan Buirchell, Birger Lindberg Moller, Dan Staerk
Summary: This study investigated the root bark extract of the plant Eremophila longifolia and identified 12 previously unreported serrulatane diterpenoids. The structures of these compounds were determined through analysis techniques and NMR analysis. The study also found that some of these compounds exhibited weak inhibitory activity against targets important for managing type 2 diabetes.
Article
Multidisciplinary Sciences
Nikolaj Lervad Hansen, Louise Kjaerulff, Quinn Kalby Heck, Victor Forman, Dan Staerk, Birger Lindberg Moller, Johan Andersen-Ranberg
Summary: This study reports the identification and characterization of a group of cytochrome P450s in the medicinal plant Tripterygium wilfordii and their function in catalyzing the formation of triptonide. The authors demonstrate the biosynthesis pathway of triptonide and successfully produce triptonide in heterologous hosts. This finding lays the foundation for the production of diterpenoid triepoxides via fermentation.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Sune Schubert, Kay Schaller, Jenny Arnling Baath, Cameron Hunt, Kim Borch, Kenneth Jensen, Jesper Brask, Peter Westh
Summary: Bioprocessing of polyester waste is a promising approach for achieving a cyclic plastic economy. This study focuses on the enzymatic breakdown of poly(ethylene terephthalate) (PET) and reveals the crucial role of endo-lytic activity in overall enzyme performance. The release of soluble PET fragments with two or three aromatic rings through endo-lytic activity leads to efficient breakdown of the polymer in aqueous bulk, contributing to the formation of monoaromatic products.
Article
Agronomy
Galaihalage K. S. Ananda, Sally L. Norton, Eve Barnes, Agnelo Furtado, Birger Lindberg Moller, Roslyn Gleadow, Robert J. Henry
Summary: In this study, the variation of grain size related genes in wild Sorghum was analyzed, revealing high morphological diversity in wild sorghum species. Six candidate genes related to grain size showed polymorphism, which may contribute to understanding and engineering grain size in sorghum and other cereals.
GENETIC RESOURCES AND CROP EVOLUTION
(2023)
Article
Biochemistry & Molecular Biology
Rita Del Giudice, Nicolo Paracini, Tomas Laursen, Clement Blanchet, Felix Roosen-Runge, Marite Cardenas
Summary: This study expands the toolkit of lipid and detergent combinations that allow the formation of stable bicelles. Systematic sample characterization using various techniques provides a set of conditions under which bicelles can be successfully formed.
Article
Plant Sciences
Silas B. Mellor, James B. Y. H. Behrendorff, Johan O. Ipsen, Christoph Crocoll, Tomas Laursen, Elizabeth M. J. Gillam, Mathias Pribil
Summary: Photosynthetic organelles, such as chloroplasts in plants, can convert solar energy into chemical energy, making them ideal for engineering small molecule bioproduction. This study explores the potential of using plant chloroplasts to produce indoxyl-beta-D-glucoside (indican), a precursor of indigo dye, by introducing an engineered biosynthetic pathway. The researchers demonstrate that P450 enzymes can function in chloroplasts and optimize the design to improve productivity. Furthermore, they find that increasing tryptophan supply does not enhance indican production, suggesting that P450 activity is the limiting factor. These findings have implications for metabolic engineering in photosynthetic hosts for the production of valuable chemicals or drug metabolites.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Microbiology
Ana Lago-Maciel, Tue K. Nielsen, Kenneth Jensen, Mette H. Nicolaisen, Rosanna C. Hennessy
Summary: We report the complete genome sequence of a potential polyethylene terephthalate (PET)-degrading bacterium, Sphingopyxis sp. strain PET50, isolated from compost.
MICROBIOLOGY RESOURCE ANNOUNCEMENTS
(2023)
Article
Chemistry, Analytical
Yong Zhao, Oliver Gericke, Tuo Li, Louise Kjaerulff, Kenneth T. Kongstad, Allison Maree Heskes, Birger Lindberg Moller, Flemming Steen Jorgensen, Henrietta Venter, Sonia Coriani, Susan J. Semple, Dan Staerk
Summary: The development of sustainable and safe drugs to combat emerging health pandemics requires new analytical technologies to explore the unique chemical properties in Nature. In this study, a new analytical technology called polypharmacology-labeled molecular networking (PLMN) was introduced, which combined positive and negative ionization tandem mass spectrometry with polypharmacological high-resolution inhibition profiling data. By applying PLMN analysis to the crude extract of Eremophila rugosa, the antihyperglycemic and antibacterial constituents were identified, revealing their activity in different assays. Furthermore, 27 new non canonical nerylneryl diphosphate-derived diterpenoids were discovered, with serrulatane ferulate esters showing potential antihyperglycemic and antibacterial activities, including synergy with oxacillin in methicillin-resistant Staphylococcus aureus strains and saddle-shaped binding to the active site of protein tyrosine phosphatase 1B. PLMN holds promise for polypharmacological natural-products-based drug discovery.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Thore B. Thomsen, Sune Schubert, Cameron J. Hunt, Kim Borch, Kenneth Jensen, Jesper Brask, Peter Westh, Anne S. Meyer
Summary: The response of PET-hydrolases to increased substrate crystallinity (X-C) of PET leads to a decrease in reaction rate, but this effect varies for different enzymes. This study examines the influence of X-C on product release rate for six thermostable PET-hydrolases. The results show that the duration of the lag phase before product formation increases with X-C. PHL7 enzyme is efficient on amorphous PET but sensitive to increased X-C, while LCCICCG, LCC, and DuraPETase enzymes tolerate higher X-C and have activity on PET with X-C of 24.4%.
Article
Plant Sciences
Chao Liang, Chi Ndi, Louise Kjaerulff, Susan Semple, Bevan Buirchell, Sonia Coriani, Birger Lindberg Moller, Dan Staerk
Summary: Extracts of Eremophila phyllopoda subsp. phyllopoda exhibited inhibitory activity against alpha-glucosidase and PTP1B. Through high-resolution profiling, 21 new serrulatane diterpenoids and five known furofuran lignans were identified. The structures were elucidated using HRMS and NMR spectroscopic data. The compounds showed potential as inhibitors for alpha-glucosidase and PTP1B.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Microbiology
Clodagh M. Carr, Malene B. Keller, Bijoya Paul, Sune W. Schubert, Kristine S. R. Clausen, Kenneth Jensen, David J. Clarke, Peter Westh, Alan D. W. Dobson
Summary: The successful degradation of polyester substrates through enzymatic processes has led to global research on bio-based treatments for plastic waste. Marine-associated microorganisms, particularly SM14est from Streptomyces sp. SM14, have shown promise as a source of polyester-degrading enzymes, specifically for the synthetic polymer PET. SM14est displayed a preference for high salt conditions, and its PET hydrolysis activity increased significantly with the addition of sodium chloride. Sequence alignment and structural comparison revealed that SM14est shares common features with key players in PET hydrolysis, such as PHL7 and IsPETase.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Yong Zhao, Nikolaj L. Hansen, Yao-Tao Duan, Meera Prasad, Mohammed S. Motawia, Birger L. Moller, Irini Pateraki, Dan Staerk, Soren Bak, Karel Miettinen, Sotirios C. Kampranis
Summary: Researchers have identified a compound called celastrol in the roots of Tripterygium wilfordii, which has potential as an effective treatment for obesity. They have also developed a synthetic method for celastrol, allowing it to be produced from table sugar. This study demonstrates the successful combination of plant biochemistry, metabolic engineering, and chemistry for the scalable synthesis of complex specialized metabolites.
Article
Plant Sciences
Chao Liang, Chi Ndi, Louise Kjaerulff, Susan Semple, Bevan Buirchell, Sonia Coriani, Birger Lindberg Moller, Dan Staerk
Summary: Extracts of Eremophila phyllopoda subsp. phyllopoda demonstrated inhibitory activity against alpha-glucosidase and PTP1B. Through extensive analysis, 21 previously undescribed serrulatane diterpenoids, two known serrulatane diterpenoids, and five known furofuran lignans were identified. These compounds showed potential as inhibitors against alpha-glucosidase and PTP1B.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Biochemical Research Methods
Bartlomiej M. Kolaczkowski, Olga V. Moroz, Elena Blagova, Gideon J. Davies, Marie Sofie Moller, Anne S. Meyer, Peter Westh, Kenneth Jensen, Keith S. Wilson, Kristian B. R. M. Krogh
Summary: Many eukaryotic proteins are N-glycosylated with high-mannose N-glycans and alpha-1,6-mannan backbones. GH92 alpha-mannosidases release mannose residues from these N-glycans, allowing alpha-endomannanases to degrade the alpha-mannan backbone. The structure and function of a multidomain GH92 alpha-mannosidase CBM have not been characterized. This study provides insights into the structure and function of a full-length five-domain GH92 alpha-mannosidase from Neobacillus novalis, demonstrating the importance of CBMs for the overall structural integrity of the enzyme.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Trang Van Tran, Hoa Nguyen, Luyen Vu, ChangWoo Lee
Summary: Glutaredoxin 3 (Grx3) is a redox protein that maintains structural integrity and glutathione (GSH) binding capabilities across different temperatures. This study investigates the roles of specific bonds in Grx3's structure and function, and how psychrophilic Grx3 variants adapt to cold environments. The highly conserved Arg51-Asp69 salt bridge and Gln56-His63 hydrogen bond are crucial for stabilizing the structure and catalytic activity of Grx3. Psychrophilic variants of Grx3 have adapted to cold environments by reducing GSH binding and increasing structural flexibility.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Amanda Lais de Souza Coto, Arthur Alexandre Pereira, Sabrina Dorta Oliveira, Milene Nobrega de Oliveira Moritz, Arthur Moraes Franco da Rocha, Paulo Roberto Dores-Silva, Noeli Soares Melo da Silva, Ana Rita de Araujo Nogueira, Lisandra Marques Gava, Thiago Vagas Seraphim, Julio Cesar Borges
Summary: J-domain proteins form a large molecular chaperone family involved in proteostasis processes, with hDjC20 playing a vital role in mitochondria and being heavily influenced by the presence of Zn+2.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Meiling Zhang, Jiaxiang Zhang, Yan Liang, Shicheng Tian, Shuyang Xie, Tong Zhou, Qin Wang
Summary: This study determined the crystal structures of RGLG2 VWA domain in Arabidopsis thaliana, revealing that Ca2+ ions act as regulators and affect the conformational change of RGLG2-VWA domain.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Alexandra Bork, Sander H. J. Smits, Lutz Schmitt
Summary: This study reveals the structure and calcium ion binding properties of CBL1 protein, and proposes a binding model of CBL1 for Ca2+. Additionally, it provides preliminary insights into the formation of the dimer interface of CBL1.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Evgeniia V. Leisi, Andrey V. Moiseenko, Sofia S. Kudryavtseva, Denis V. Pozdyshev, Vladimir I. Muronetz, Lidia P. Kurochkina
Summary: The pathogenesis of prion diseases involves the transformation of prion protein into an insoluble form. This study found that two phage chaperonins can promote the fibrillation of prion protein in an ATP-dependent manner, resulting in the formation of less toxic large clusters. These fibrils differ in morphology and properties from those formed spontaneously in acidic pH with denaturants.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Gaurab Chowdhury, Saroj Biswas, Yuthika Dholey, Puja Panja, Sumit Das, Subrata Adak
Summary: Magnesium is an important divalent cation for regulating enzyme activity. The binding of Mg2+ through the PAS domain inhibits phosphoglycerate kinase (PGK) activity in LmPAS-PGK at neutral pH, but PGK activity is derepressed at acidic pH. Mutation studies revealed that the Asp-4 residue is crucial for Mg2+ binding at neutral pH.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Shima Ghaedizadeh, Majid Zeinali, Bahareh Dabirmanesh, Behnam Rasekh, Khosrow Khajeh, Ali Mohammad Banaei-Moghaddam
Summary: Implementing hyperthermostable carbonic anhydrases into CO2 capture and storage technologies can increase the rate of CO2 absorption from industrial flue gases. This study successfully improved the thermostability of a known hyperthermostable carbonic anhydrase through rational engineering of a single-point mutation.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Khaled A. Elnahriry, Dorothy C. C. Wai, Lauren M. Ashwood, Muhammad Umair Naseem, Tibor G. Szanto, Shaodong Guo, Gyorgy Panyi, Peter J. Prentis, Raymond S. Norton
Summary: Sea anemone venom contains a peptide called Tst2, which shows sequence similarity to peptides that interact with various ion channels. Recombinant Tst2 was successfully produced and its structure and function were studied. The results showed that Tst2 is an inhibitor of the TRPV1 channel.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
