Article
Plant Sciences
Shmuel Galili, Joseph Hershenhorn, Marvin Edelman, Vladimir Sobolev, Evgeny Smirnov, Orit Amir-Segev, Aharon Bellalou, Evgenia Dor
Summary: Chickpea is an important crop in Israel, but sensitive to imidazolinone herbicides. A chickpea line resistant to these herbicides was developed using chemical mutagenesis, with a point mutation detected in one of the genes encoding the AHAS catalytic subunit. The mutation provided resistance to a specific group of herbicides and showed single-gene semi-dominant inheritance pattern, as confirmed by genetic transformation in tobacco plants.
Article
Biochemistry & Molecular Biology
Lucie Meyer, Fanny Pernin, Severine Michel, Geraldine Bailly, Bruno Chauvel, Valerie Le Corre, Christophe Delye
Summary: Assessing the capacity of weeds to develop herbicide resistance before it occurs in the field is crucial for effective chemical weed control. This study used herbicide selection and controlled crosses to accelerate the evolution of resistance to two commonly used herbicides in Ambrosia artemisiifolia. The results showed that non-target-site-based resistance (NTSR) to herbicides was significantly increased in just two generations of selection. NTSR to the tested herbicides emerged and was reinforced in subsequent generations. Further bioassays confirmed the emergence of resistance to imazamox and/or tribenuron in multiple A. artemisiifolia populations. NTSR was found to be the predominant type of resistance, with only one population showing a mutant ALS allele in addition to NTSR. This study highlights the importance of pre-emptive assessment of resistance evolution in weed populations.
Article
Agriculture, Multidisciplinary
Hudson K. Takano, Zoltan L. Benko, Moriah M. Zielinski, Adel Hamza, Christopher A. Kalnmals, Joshua J. Roth, Karla Bravo-Altamirano, Thomas Siddall, Norbert Satchivi, Jeffrey B. Church, Dilpreet S. Riar
Summary: Herbicides are effective tools for managing weeds and ensuring food production. Corteva Agriscience R&D has discovered new diphenyl-ether compounds with excellent postemergent efficacy on important weed species and corn safety. Through research in chemistry, biology, biochemistry, and computational modeling, the primary mode of action for these compounds was elucidated as targeting the acetolactate synthase (ALS) enzyme. These compounds have a unique biochemical profile and show excellent herbicidal activity and corn selectivity, making them a significant development in the search for novel, safe, and sustainable weed control solutions.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Ane Valera, Shan Wang, Reuben Carr, Laurent Trembleau, Hai Deng
Summary: The biochemical characterization of a new KARI (MtKARI-II) from a Mycobacterium tuberculosis variant with a similar kinetic profile to class I KARIs is reported here. Phylogenetic analysis suggests that MtKARI-II is clustered into a class II KARI superfamily.
Article
Agronomy
Yue Guo, Changle Liu, Weihua Long, Jianqin Gao, Jiefu Zhang, Song Chen, Huiming Pu, Maolong Hu
Summary: With the increasing promotion of simplified rapeseed cultivation, the development of cultivars with high resistance to herbicides is urgently needed. In this study, a novel mutant DS3 with high sulfonylurea resistance was obtained through ethyl methane sulfonate mutagenesis. The mutant harbored two mutations in the acetohydroxyacid synthase (AHAS) genes and showed a synergistic effect that greatly increased herbicide resistance.
Article
Biotechnology & Applied Microbiology
Tatsuya Kato, Mai Kano, Ami Yokomori, Junya Azegami, Hesham A. El Enshasy, Enoch Y. Park
Summary: The mitochondrial membrane potential of the riboflavin-overproducing Ashbya gossypii mutant was decreased compared to the wild type strain, resulting in increased reactive oxygen species. It was discovered that flavoproteins and branched-chain amino acids play crucial roles in riboflavin production.
MICROBIAL CELL FACTORIES
(2023)
Article
Plant Sciences
Norazua Zakaria, Rabiatuladawiyah Ruzmi, Salmah Moosa, Norhayu Asib, Dzarifah Zulperi, Siti Izera Ismail, Muhammad Saiful Ahmad-Hamdani
Summary: This study revealed the resistance mechanism of L. flava population to AHAS inhibitors, showing that this aquatic weed has developed resistance to these herbicides.
PHYSIOLOGY AND MOLECULAR BIOLOGY OF PLANTS
(2021)
Article
Chemistry, Multidisciplinary
Wang Baifan, He Yinwu, Wen Xin, Niu Congwei, Xi Zhen
Summary: Flumetsulam is a widely used herbicide targeting AHAS, but mutations in AHAS can cause herbicide resistance. This study established a method called MB-QSAR to quantitatively predict drug resistance caused by mutations in AHAS and elucidate the structure-resistance relationships. The MB-QSAR model showed excellent correlation between experimental and computational data, providing good predictions for the inhibition properties of flumetsulam against AHAS mutants. The model also provided insight into potential positions for herbicide resistant mutations and guidance for modifying and designing new resistance-evading herbicides.
ACTA CHIMICA SINICA
(2022)
Article
Agronomy
Mauricio Alfredo Tcach, Alejandra Mabel Landau, Alex Montenegro, Daniel Diaz, Carlos Acuna, Alberto Raul Prina
Summary: A new mutation conferring tolerance to IMI in cotton was isolated in this research, showing promising potential for the development of commercial cotton cultivars with IMI tolerance. The mode of inheritance of this trait was determined, and field assays confirmed the increased tolerance of the mutant line compared to non-tolerant genotypes.
Article
Agriculture, Multidisciplinary
Tao Wei, Xin Wen, Congwei Niu, Sijing An, Dawei Wang, Zhen Xi, Ning Ning Wang
Summary: The development of herbicide-resistant germplasm through gene editing techniques holds great significance in solving the weed problem in crop fields. This study successfully created herbicide-resistant genotypes and found a correlation between the resistance levels of gene-edited plants and prediction models.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Agronomy
Axelle Koreki, Severine Michel, Caroline Lebeaux, Lidwine Trouilh, Christophe Delye
Summary: This study investigates the prevalence, mode of evolution, and spread of resistance-endowing ALS alleles in corn poppy populations in France. With the use of massively parallel amplicon sequencing, it was found that mutant ALS alleles have complex geographic distributions, which could be attributed to large population sizes, multiple independent mutation events, and human-mediated spread of resistance. The study also reveals that mutant ALS alleles are associated with resistance to the synthetic auxin 2,4-D.
PEST MANAGEMENT SCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Juthamas Jaroensuk, Litavadee Chuaboon, Chatchai Kesornpun, Pimchai Chaiyen
Summary: The resistance of pathogens to antibiotics is a major threat to global health, and new antibiotic targets are needed to develop alternative drugs. Enzymes involved in the biosynthesis of riboflavin and flavin cofactors (FMN/FAD) are attractive targets as they are necessary for most bacteria but not present in humans. This review discusses the current knowledge of these enzymes and the FMN riboswitch, highlighting recent progress in understanding their structures, mechanisms, and potential as antibiotic targets.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Jia-hui Li, Yan Wang, Yun-peng Wu, Ran-hong Li, Shuang Liang, Jing Zhang, Yong-gang Zhu, Bei-jie Xie
Summary: Based on the pharmacophore binding strategy and the principle of bioelectronic isobaric, a series of novel thiourea compounds containing aromatic-substituted pyrimidines were designed and synthesized using the sulfonylurea bridge as the parent structure. Some compounds showed good herbicidal activity, especially compounds 4d and 4f, which exhibited higher comparative activity than the commercial herbicide bensulfuron-methyl. The preliminary structure-activity relationship (SAR) and in vivo AHAS enzyme activity inhibition experiments further confirmed the activity of these compounds.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Sitong Yan, Xiaoxiong Lin, Zhenhao Wen, Junping Xiao, Huangbing Liang, Yali Liu, Mingliang Wang, Caizhen Zhu, Jian Xu
Summary: New sulfonylurea inhibitors with high efficacy and fast hydrolysis degradation rate were designed based on commercial product Chlorimuron-Ethyl, using quantum mechanical approach to estimate binding interaction and calculate hydrolysis energy barrier. The designed compounds I1 and I2, with an amino group at the fourth position of benzene ring, exhibited excellent herbicidal activity and rapid degradation. This study provides insights for developing potential herbicidal candidates for sustainable environmental and ecological development.
JOURNAL OF COMPUTATIONAL BIOPHYSICS AND CHEMISTRY
(2021)
Article
Agronomy
Lei Chen, Gang Gu, Chengxu Wang, Zhufeng Chen, Wei Yan, Man Jin, Gang Xie, Junli Zhou, Xing Wang Deng, Xiaoyan Tang
Summary: Herbicide resistance is valuable for integrated weed management in agriculture, particularly in rice fields where weedy rice poses a challenge. This study obtained three mutant variants of the OsALS gene in rice through ethyl methyl sulfonate mutagenesis, with W-548 M mutant showing high levels of resistance to a broad spectrum of herbicides. The stable inheritance of herbicide resistance in rice lines makes W-548 M mutation a valuable resource for breeding herbicide resistant rice and weed management.
Article
Biochemistry & Molecular Biology
Gry Brandt Boe-Hansen, Joao Paulo A. Rego, Nana Satake, Bronwyn Venus, Pawel Sadowski, Amanda Nouwens, Yutao Li, Michael McGowan
MOLECULAR REPRODUCTION AND DEVELOPMENT
(2020)
Article
Multidisciplinary Sciences
Thierry Lonhienne, Yu Shang Low, Mario D. Garcia, Tristan Croll, Yan Gao, Quan Wang, Lou Brillault, Craig M. Williams, James A. Fraser, Ross P. McGeary, Nicholas P. West, Michael J. Landsberg, Zihe Rao, Gerhard Schenk, Luke W. Guddat
Article
Neurosciences
Matthew D. Figley, Weixi Gu, Jeffrey D. Nanson, Yun Shi, Yo Sasaki, Katie Cunnea, Alpeshkumar K. Malde, Xinying Jia, Zhenyao Luo, Forhad K. Saikot, Tamim Mosaiab, Veronika Masic, Stephanie Holt, Lauren Hartley-Tassell, Helen Y. McGuinness, Mohammad K. Manik, Todd Bosanac, Michael J. Landsberg, Philip S. Kerry, Mehdi Mobli, Robert O. Hughes, Jeffrey Milbrandt, Bostjan Kobe, Aaron DiAntonio, Thomas Ve
Summary: SARM1 is a nicotinamide adenine dinucleotide (NAD+)-cleaving enzyme that is activated by an increase in the ratio of NMN to NAD+, triggering axon destruction. The structural analysis showed that both NMN and NAD+ compete for binding to the auto inhibitory N-terminal armadillo repeat (ARM) domain of SARM1.
Article
Food Science & Technology
Daniel Dashevsky, Darin Rokyta, Nathaniel Frank, Amanda Nouwens, Bryan G. Fry
Summary: The genus Calliophis is the most basal branch of the family Elapidae, with some species developing highly elongated venom glands. Recent research has shown that C. bivirgatus has evolved a seemingly unique toxin that produces spastic paralysis in prey by acting on voltage-gated sodium channels. The broader clade of C. bivirgatus toxins contains a variety of toxins including classic elapid eight-cysteine three-finger toxins and delta-elapitoxins, with some similarities to cytotoxins from other elapids, but those characterized are not cytotoxic and show no clear relationships to toxins of known function from other species.
Article
Biochemistry & Molecular Biology
Tehseen Rubbab, Cassandra L. Pegg, Toan K. Phung, Amanda S. Nouwens, K. Y. Benjamin Yeo, Lucia F. Zacchi, Amna Muhammad, S. M. Saqlan Naqvi, Benjamin L. Schulz
Summary: The University of Queensland, School of Chemistry and Molecular Biosciences Mass Spectrometry Facility provided assistance and expertise. This work was supported by a grant from the HEC Pakistan to Tehseen Rubbab under the International Research Support Initiative Program.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Liping Liu, Richard M. Lucas, Jeffrey D. Nanson, Yan Li, Jason Whitfield, James E. B. Curson, Neeraj Tuladhar, Kirill Alexandrov, Mehdi Mobli, Matthew J. Sweet, Bostjan Kobe, Jennifer L. Stow, Lin Luo
Summary: In this study, we identify a novel immune-specific Syk scaffold protein SCIMP, which can contribute to inflammation through selective TLR-driven inflammatory responses.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Thierry Lonhienne, Yan Cheng, Mario D. Garcia, Shu Hong Hu, Yu Shang Low, Gerhard Schenk, Craig M. Williams, Luke W. Guddat
Summary: Acetohydroxyacid synthase (AHAS) is the target of more than 50 commercial herbicides, with many site-of-action resistance isolates identified in weeds. The mutations at P197 and W574 of AHAS can reduce the binding affinity of herbicides and abolish time-dependent accumulative inhibition. However, the bulky herbicide bispyribac is able to counteract the detrimental effects of these mutations, explaining the absence of site-of-action resistance to this herbicide.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Biswaranjan Mohanty, Julien Orts, Geqing Wang, Stefan Nebl, Wesam S. Alwan, Bradley C. Doak, Martin L. Williams, Begona Heras, Mehdi Mobli, Martin J. Scanlon
Summary: The structures of protein-ligand complexes are crucial for drug design, and are mainly determined using X-ray crystallography. However, when crystallography fails, NMR is often used as an alternative method. Unfortunately, the tools available for rapid and robust structure determination of protein-ligand complexes by NMR are currently limited. In this study, the NMR2 approach is described, which allows the determination of the binding pose of a small molecule in a weak protein-ligand complex by collecting sparse protein methyl-to-ligand NOEs from a selectively labeled protein sample and an unlabeled ligand. This approach extends the utility of NMR2 to larger protein-ligand complexes.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Michael D. Healy, Joanna Sacharz, Kerrie E. McNally, Calum McConville, Vikas A. Tillu, Ryan J. Hall, Molly Chilton, Peter J. Cullen, Mehdi Mobli, Rajesh Ghai, David A. Stroud, Brett M. Collins
Summary: SNX17 controls the endosomal recycling of transmembrane cargo proteins through its association with the Commander trafficking complex and the PDLIM family of proteins. The interaction between SNX17 and PDLIM is mediated by a unique peptide interaction involving electrostatic contacts and a conserved proline-containing loop sequence. This interaction may play a role in regulating the activity of SNX17 in conjunction with Commander and actin-rich endosomal trafficking domains.
Article
Biochemistry & Molecular Biology
Junyu Liu, Michael Maxwell, Thom Cuddihy, Theo Crawford, Madeline Bassetti, Cameron Hyde, Steve Peigneur, Jan Tytgat, Eivind A. B. Undheim, Mehdi Mobli
Summary: Receptor avidity through multivalency is difficult to engineer in synthetic molecules, but can be found in natural bivalent antibodies. The discovery of bivalent venom peptides with tandem repeat domains has provided insight into multivalency in biomolecules. ScrepYard, an online resource, assists in identifying SCREP sequences and characterizing this emerging class of biomolecules.
Article
Biochemical Research Methods
Qiushi Cao, Cheng Ge, Xuejie Wang, Peta J. Harvey, Zixuan Zhang, Yuan Ma, Xianghong Wang, Xinying Jia, Mehdi Mobli, David J. Craik, Tao Jiang, Jinbo Yang, Zhiqiang Wei, Yan Wang, Shan Chang, Rilei Yu
Summary: With the rise of multidrug-resistant bacteria, antimicrobial peptides (AMPs) have emerged as potential alternatives to traditional antibiotics for treating bacterial infections. However, traditional methods of discovering and designing AMPs are time-consuming and costly. This study utilized deep learning techniques, including sequence generative adversarial nets, bidirectional encoder representations from transformers, and multilayer perceptron, to design and identify AMPs. Six candidate AMPs were then screened and one of them, A-222, showed inhibition against both gram-positive and gram-negative bacteria. Structural analysis and subsequent structure-activity relationship studies led to the design of peptide analogs with increased activity against specific bacteria. Overall, deep learning holds great promise in accelerating the discovery of novel AMPs and could have significant implications in developing new antimicrobial treatments.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Chemistry, Medicinal
Christian R. O. Bartling, Flora Alexopoulou, Sarah Kuschert, Yanni K. -Y. Chin, Xinying Jia, Vita Sereikaite, Dennis Ozcelik, Thomas M. Jensen, Palash Jain, Mads M. Nygaard, Kasper Harpsoe, David E. Gloriam, Mehdi Mobli, Kristian Stromgaard
Summary: Peptides targeting disease-relevant protein-protein interactions have limitations in terms of metabolic stability and membrane permeability. Peptide cyclization, particularly hydrocarbon stapling, offers a valuable approach to develop metabolically stable and cell-permeable cyclic leads with improved affinity and stability. In this study, a comprehensive examination of cyclization strategies led to the identification of cyclic APP dodecamer peptides that target the phosphotyrosine binding domain of Mint2 with significantly improved properties.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Polymer Science
Maria Eduarda Sevilla, Mario D. D. Garcia, Yunierkis Perez-Castillo, Vinicio Armijos-Jaramillo, Santiago Casado, Karla Vizuete, Alexis Debut, Liliana Cerda-Mejia
Summary: Due to the lack of efficient treatment of plastic waste, extensive plastic production has become a serious environmental and health problem. This study focuses on the enzymatic degradation of PET by IsPETase, a cutinase-like enzyme, to completely break down the polymer. Through rational design and mutation of the active site, the researchers were able to enhance the PET-degrading activity of IsPETase, particularly with the S238Y mutant. The modified enzyme showed a 3.3-fold increase in degradation activity compared to the wild-type enzyme and was capable of breaking down highly crystalline PET found in commercial soft drink bottles.
Article
Chemistry, Multidisciplinary
Xinying Jia, Yanni K. -Y. Chin, Alan H. H. Zhang, Theo Crawford, Yifei Zhu, Nicholas L. L. Fletcher, Zihan Zhou, Brett R. R. Hamilton, Martin Stroet, Kristofer J. J. Thurecht, Mehdi Mobli
Summary: The authors report the engineering of self-cyclizing 'autocyclase' proteins to generate macrocyclic peptides and proteins with favorable reaction kinetics for suppressing polymerization. Macrocyclisation of proteins and peptides results in a remarkable increase in structural stability, making cyclic peptides and proteins of great interest in drug discovery. The engineering of a self-cyclising autocyclase protein provides a simple, alternative way to access a vast diversity of macrocyclic biomolecules.
COMMUNICATIONS CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Gagan Sharma, Carolyne B. Braga, Kai-En Chen, Xinying Jia, Venkatraman Ramanujam, Brett M. Collins, Roberto Rittner, Mehdi Mobli
Summary: Chlorotoxin (ClTx) is a disulfide-rich peptide isolated from scorpion venom that selectively binds to brain tumors and has emerged as a potential target for the vascular endothelial growth factor receptor, neuropilin-1 (NRP1). This study characterized the binding details of ClTx to NRP1 through NMR spectroscopy, revealing a non-standard binding motif that provides a basis for future engineering of ClTx for improved applications.
CURRENT RESEARCH IN STRUCTURAL BIOLOGY
(2021)