Article
Biotechnology & Applied Microbiology
Andrea L. Livieri, Facundo Colaccini, Martin A. Hernandez, Gabriela Gago, Hector M. Alvarez, Hugo Gramajo, Eduardo Rodriguez
Summary: In actinomycetes, acyl-CoA carboxylases (ACCs) are biotin-dependent enzymes with diverse structures and functions. Rhodococcus jostii RHA1 was found to have multiple putative ACC domains and subunits. Mutant strains with specific genes disrupted showed the importance of these genes in lipid biosynthesis and growth.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Agriculture, Multidisciplinary
Buli Su, Peixuan Lai, Fan Yang, Anzhang Li, Ming-Rong Deng, Honghui Zhu
Summary: This study developed a novel method to increase the supply of acetyl-CoA in Saccharomyces cerevisiae and improve the production of downstream products. By optimizing metabolic pathways and conducting genetic engineering, the production of mevalonic acid was successfully increased, and further improvement was achieved by dynamically downregulating gene expression. The final strain produced a high yield of lycopene.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Geriatrics & Gerontology
Amy Zheng, Seong Eun Kwak, Jesper B. Birk, Edward B. Arias, Dominic Thorley, Jorgen F. P. Wojtaszewski, Gregory D. Cartee
Summary: This study investigated the impact of caloric restriction (CR) on AMP-activated protein kinase (AMPK) and its substrates in skeletal muscle of older animals. The results revealed that CR significantly increased the phosphorylation of AMPK and several AMPK substrates, suggesting a potential role of AMPK in the antiaging effects of CR.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Microbiology
Pan Wang, Xin Wang, Ying Yin, Mingliang He, Wei Tan, Wenting Gao, Jianping Wen
Summary: The study found that inactivating the signal transduction protein GlnB can increase the production of ascomycin by enhancing the supply of precursors. Protein co-precipitation experiments and coupled enzyme activity assays revealed that the interaction between GlnB protein and the alpha subunit of acetyl-CoA carboxylase and propionyl-CoA carboxylase inhibited their activities.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Chemistry, Medicinal
Tonghui Huang, Xin Wu, Shirong Yan, Tianya Liu, Xiaoxing Yin
Summary: A series of spiroketopyrazole derivatives were synthesized and evaluated for their anticancer activities as ACC inhibitors. Compound 7j showed the strongest enzyme inhibitory activity, while compound 7m exhibited potent anti-proliferative effects against various cancer cell lines, indicating its potential as a therapeutic agent for hepatocellular carcinoma.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Microbiology
John E. Cronan
Summary: This review provides an update on the research of Escherichia coli acetyl-CoA carboxylase (ACC), focusing on the structures, stoichiometry, regulation of ACC activity and expression.
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS
(2021)
Article
Biochemistry & Molecular Biology
Ryo Mizojiri, Daisuke Tomita, Masako Sasaki, Yoshihiko Satoh, Yukiko Yamamoto, Hiroyuki Sumi, Hironobu Maezaki
Summary: By modifying the molecular length, a new ACC1-selective inhibitor 1i was discovered. Further chemical modification produced compound 1n with potent ACC1 selective inhibition and suitable PK profile for in vivo evaluations. This novel series of potent ACC1-selective inhibitors shows promise as both research tools and potential therapeutic agents.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Fei-Yuan Yu, Qian Xu, Qi-Yao Wei, Hai-Ying Mo, Qiu-Hua Zhong, Xiao-Yun Zhao, Andy T. Y. Lau, Yan-Ming Xu
Summary: ACC2 is under-expressed in cancerous tissue and negatively correlated with tumor size, lymph-node metastases, and clinical stage in lung adenocarcinoma. Knocking down ACC2 promotes cell proliferation and migration, and affects the expression of cell cycle-related genes. Lung adenocarcinoma patients with under-expressed ACC2 have a worse prognosis.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2022)
Article
Microbiology
Tianyu Chen, Jing Yao, Keao Quan, Jingchen Xu, Xudong Hang, Qian Tong, Genyan Liu, Peipei Luo, Liping Zeng, Ganzhu Feng, Hongkai Bi
Summary: This study investigates the antifungal efficacy of firsocostat against Candida albicans. The combination of firsocostat with other antifungal agents shows synergistic effects in drug-sensitive and drug-resistant C. albicans strains. The study also demonstrates that firsocostat directly binds to C. albicans ACC and inhibits its enzymatic activity. These findings suggest that repurposing firsocostat holds promising potential in antifungal drug development and candidiasis treatment.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Siraprapa Siritutsoontorn, Witchuda Sukjoi, Steven W. Polyak, Chareeporn Akekawatchai, Sarawut Jitrapakdee
Summary: HLCS plays a crucial role in breast cancer growth and migration by promoting the biotinylation of carboxylases. Depletion of biotin or reduced expression of HLCS inhibits cell proliferation and migration, leading to apoptosis in breast cancer cells.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Wenyu Wu, Ruilin Chen, Yuanda Wan, Liren Li, Jiajia Han, Qiyun Lei, Zhipeng Chen, Shuwen Liu, Xingang Yao
Summary: Dengue fever is a common viral disease transmitted by mosquitoes, and there is a need for new drugs to combat it. Research suggests that inhibiting acetyl-CoA carboxylase (ACC) can effectively decrease the proliferation of the dengue virus and improve survival rates in infected mice.
Article
Biochemistry & Molecular Biology
Xin Wu, Yongbo Yu, Tonghui Huang
Summary: A potential ACC inhibitor was identified in this study, and a series of related compounds were synthesized for investigation, among which 6g showed the strongest ACC inhibitory activity, while 6l exhibited potent cytotoxicity. Preliminary mechanistic studies suggested that these compounds may act by reducing malonyl-CoA levels, arresting the cell cycle, and inducing apoptosis.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Biology
Sean Rogers, Hanaa Hariri, N. Ezgi Wood, Natalie Ortiz Speer, W. Mike Henne
Summary: This study reveals that yeast undergo metabolic remodeling at nucleus-vacuole junctions in response to acute glucose restriction, retaining HMGCRs and promoting mevalonate pathway flux in a spatially coordinated manner. The protein Nvj1 plays a crucial role in this process, demonstrating the importance of inter-organelle contacts in organizing metabolic reactions. Loss of HMGCR compartmentalization perturbs yeast growth following glucose starvation, indicating its role in adaptive metabolic remodeling.
Article
Food Science & Technology
Kaiyang Chen, Meimei Hu, Ming Tang, Congcong Gao, Haikuan Wang, Shuli Man, Fuping Lu
Summary: Appropriate intake of oligosaccharides can prevent obesity by regulating appetite, while butyrate consumption can alleviate obesity. The activity of acetyl-CoA carboxylase is inhibited by the conversion of butyrate to butyryl-CoA, which suggests possible obesity therapeutic targets.
FOOD RESEARCH INTERNATIONAL
(2022)
Review
Oncology
Yu Wang, Weixing Yu, Sha Li, Dingyuan Guo, Jie He, Yugang Wang
Summary: Acetyl-CoA carboxylases (ACCs) are enzymes that play important roles in fatty acid synthesis and oxidation. ACC1 and ACC2 are two members of ACCs in mammals, with ACC1 being involved in various diseases such as cancer, diabetes, and obesity. ACC1 also has the ability to influence protein post-translational modifications. Therefore, studying ACC1 can provide insights into disease treatment and the development of specific inhibitors.
FRONTIERS IN ONCOLOGY
(2022)
Article
Microbiology
Ashley M. Dungan, Leon M. Hartman, Giada Tortorelli, Roy Belderok, Annika M. Lamb, Lynn Pisan, Geoffrey I. McFadden, Linda L. Blackall, Madeleine J. H. van Oppen
Article
Biology
Christopher D. Goodman, Taher Uddin, Natalie J. Spillman, Geoffrey McFadden
Article
Immunology
Lauren E. Holz, Yu Cheng Chua, Maria N. de Menezes, Regan J. Anderson, Sarah L. Draper, Benjamin J. Compton, Susanna T. S. Chan, Juby Mathew, Jasmine Li, Lukasz Kedzierski, Zhongfang Wang, Lynette Beattie, Matthias H. Enders, Sonia Ghilas, Rose May, Thiago M. Steiner, Joshua Lange, Daniel Fernandez-Ruiz, Ana Maria Valencia-Hernandez, Taryn L. Osmond, Kathryn J. Farrand, Rebecca Seneviratna, Catarina F. Almeida, Kirsteen M. Tullett, Patrick Bertolino, David G. Bowen, Anton Cozijnsen, Vanessa Mollard, Geoffrey I. McFadden, Irina Caminschi, Mireille H. Lahoud, Katherine Kedzierska, Stephen J. Turner, Dale I. Godfrey, Ian F. Hermans, Gavin F. Painter, William R. Heath
SCIENCE IMMUNOLOGY
(2020)
Article
Biology
Amy L. Burns, Brad E. Sleebs, Ghizal Siddiqui, Amanda E. De Paoli, Dovile Anderson, Benjamin Liffner, Richard Harvey, James G. Beeson, Darren J. Creek, Christopher D. Goodman, Geoffrey I. McFadden, Danny W. Wilson
Article
Parasitology
Marco Biddau, T. R. Santha Kumar, Philipp Henrich, Larissa M. Laine, Gavin J. Blackburn, Achuthanunni Chokkathukalam, Tao Li, Kim Lee Sim, Lewis King, Stephen L. Hoffman, Michael P. Barrett, Graham H. Coombs, Geoffrey I. McFadden, David A. Fidock, Sylke Mueller, Lilach Sheiner
Summary: The study highlights the importance of redox regulation in malaria parasites and suggests LipB as a potential target for the development of new transmission drugs. Deletion of lipB in Plasmodium falciparum impacts redox regulators expression, central carbon metabolism, and development in the mosquito, suggesting a role for lipB in these processes. Further research on LA biosynthesis is needed to better understand its role in asexual stages of malaria parasites.
INTERNATIONAL JOURNAL FOR PARASITOLOGY
(2021)
Article
Plant Sciences
Andreas Holzinger, Sabrina Obwegeser, Ancuela Andosch, Ulf Karsten, Christina Oppermann, Wolfgang Ruth, Allison van de Meene, Christopher D. Goodman, Ursula Luetz-Meindl, John A. West
Summary: By investigating the ultrastructure and carbohydrate composition of the red alga Tsunamia transpacifica, insights into its adaptation to growing on plastic surfaces have been revealed. Overall, Tsunamia adapts to the uncommon habitat through a thick cell wall, multilobed chloroplast, and specific structures with adhering capacities.
Article
Biochemistry & Molecular Biology
Brodie L. Bailey, William Nguyen, Anna Ngo, Christopher D. Goodman, Maria R. Gancheva, Paola Favuzza, Laura M. Sanz, Francisco-Javier Gamo, Kym N. Lowes, Geoffrey I. McFadden, Danny W. Wilson, Benoit Laleu, Stephen Brand, Paul F. Jackson, Alan F. Cowman, Brad E. Sleebs
Summary: The study identified a triazolopyrimidine compound with good activity against Plasmodium falciparum and high selectivity against human cells, but faced challenges such as slow onset of action and low aqueous solubility. Further optimization is needed for its development as a potential partner in anti-malarial treatment.
BIOORGANIC CHEMISTRY
(2021)
Article
Parasitology
Ming Jang Chua, Jiahui Tng, Eva Hesping, Gillian M. Fisher, Christopher D. Goodman, Tina Skinner-Adams, Darren Do, Andrew J. Lucke, Robert C. Reid, David P. Fairlie, Katherine T. Andrews
Summary: Research has shown that the anticancer drug HDAC inhibitor AR-42 and its 36 analogues have in vitro activity against Plasmodium parasites, with some compounds showing low cytotoxicity to human cells and high selectivity for the parasites. AR-42 induces hyperacetylation of Plasmodium histone H4 by inhibiting PfHDAC(s), effectively blocking parasite growth inside red blood cells and demonstrating curative properties in oral treatment of experimental mouse malaria.
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2021)
Review
Microbiology
Hayley D. Buchanan, Christopher D. Goodman, Geoffrey I. McFadden
Summary: This article discusses the roles of a crucial cellular compartment, the apicoplast, in the different stages of the malaria parasite's life cycle, with a focus on two species of Plasmodium.
JOURNAL OF EUKARYOTIC MICROBIOLOGY
(2022)
Article
Immunology
Ana Maria Valencia-Hernandez, Thomas Zillinger, Zhengyu Ge, Peck S. Tan, Anton Cozijnsen, Geoffrey I. McFadden, Mireille H. Lahoud, Irina Caminschi, Winfried Barchet, William R. Heath, Daniel Fernandez-Ruiz
Summary: Tissue resident memory T cells (TRM cells) play a crucial role in tissue surveillance and rapid response to infection. This study explores the potential of various adjuvants targeting different pathogen recognition receptors to induce CD8' TRM formation. CpG oligodeoxynucleotides (ODN) were found to be the most efficient inducers of liver TRM cells among all tested adjuvants. Additionally, combining CpG ODN with cationic liposome DOTAP further enhances their potency. This study provides valuable insights for the development of liver TRM-based vaccines.
Article
Immunology
Amy L. Burns, Brad E. Sleebs, Maria Gancheva, Kimberley T. McLean, Ghizal Siddiqui, Henrietta Venter, James G. Beeson, Ryan O'Handley, Darren J. Creek, Shutao Ma, Sonja Froelich, Christopher D. Goodman, Geoffrey McFadden, Danny W. Wilson
Summary: This study evaluated azithromycin analogues and found that they improved quick-killing activity against Plasmodium falciparum and Plasmodium knowlesi parasites. These analogues not only maintained activity, but also had higher selectivity against P. falciparum compared to human cells. The quick-killing activity of these drugs was achieved by inhibiting bacterium-like ribosomes or the apicoplast, and their activity did not improve in other related parasites and bacteria. This research provides new starting points for developing azithromycin analogues with quick-killing antimalarial activity.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Madeline Dans, Henni Piirainen, William D. Nguyen, Sachin T. Khurana, Somya Mehra, Zahra Razook, Niall K. Geoghegan, Aurelie Dawson, Sujaan R. Das, Molly Parkyn J. Schneider, Thorey Jonsdottir, Mikha Gabriela, Maria I. Gancheva, Christopher W. Tonkin, Vanessa L. Mollard, Christopher Dean E. Goodman, Geoffrey S. McFadden, Danny F. Wilson, Kelly E. Rogers, Alyssa Barry, Brendan R. Crabb, Tania de Koning-Ward, Brad Sleebs, Inari Kursula, Paul Gilson
Summary: New antimalarial drugs targeting Plasmodium falciparum have been identified by studying drug resistance. Mutations in two genes were engineered in wild-type parasites using CRISPR-Cas9, which rendered the parasites resistant to the drugs. The drugs were found to inhibit actin polymerisation, which is essential for the invasion of red blood cells by the parasites.
Article
Ecology
Keren Maor-Landaw, Marion Eisenhut, Giada Tortorelli, Allison van de Meene, Samantha Kurz, Gabriela Segal, Madeleine J. H. van Oppen, Andreas P. M. Weber, Geoffrey I. McFadden
Summary: The symbiotic partnership between corals and dinoflagellate algae is crucial for coral reefs. The transporter protein BmSWEET1 in dinoflagellate cells is responsible for transferring glucose from algae to the host coral tissue, providing the necessary energy for coral reefs. This study provides insights into the mechanism of nutrient exchange in coral-algae symbiosis.
ISME COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
