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
Biochemistry & Molecular Biology
Jason J. Hu, Jane K. J. Lee, Yun-Tao Liu, Clinton Yu, Lan Huang, Inna Aphasizheva, Ruslan Aphasizhev, Z. Hong Zhou
Summary: 3-methylcrotonyl-CoA carboxylase (MCC) is a biotin-dependent mitochondrial enzyme involved in leucine catabolism. We discovered that native MCC from Leishmania tarentolae (LtMCC) forms filaments and determined their structures. The filaments are composed of a6b6 LtMCCs stacked together, binding biotin non-covalently and lacking coenzyme A. The stacking immobilizes the biotin carboxylase domains, rendering the enzyme inactive. Our findings propose a new catalysis model for LtMCC and provide insights into polymerization in the carboxylase superfamily.
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
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
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
Biochemistry & Molecular Biology
Yujun Han, Ying Sun, Hong Ma, Ruolin Wang, Yuning Lan, Haifeng Gao, Zhaofeng Huang
Summary: Wild oat is a common and problematic weed in wheat fields in China, and controlling it has become increasingly difficult. This study aimed to identify the molecular basis of clodinafop-propargyl resistance in wild oat. Two resistant populations were found to have high resistance to fenoxaprop-p-ethyl, low resistance to clethodim and pinoxaden, but they were sensitive to mesosulfuron-methyl and pyroxsulam. An Ile2041-Asn mutation was identified in both resistant plants. The resistant populations also showed metabolic resistance, which was confirmed by the application of inhibitors.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(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)
Article
Biochemistry & Molecular Biology
Takaya Saito, Paul Whatmore, John F. Taylor, Jorge M. O. Fernandes, Anne-Catrin Adam, Douglas R. Tocher, Marit Espe, Kaja H. Skjaerven
Summary: Micronutrients play important roles in growth and metabolism, with studies indicating that increased levels of certain B-vitamins and microminerals are needed when using plant-based diets. Micronutrient supplementation affects hepatic gene expression and DNA methylation levels, showing an important role in lipid metabolism through epigenetic control of gene expression.
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
Gastroenterology & Hepatology
Marcos F. Fondevila, Uxia Fernandez, Maria J. Gonzalez-Rellan, Natalia Da Silva Lima, Xabier Buque, Agueda Gonzalez-Rodriguez, Cristina Alonso, Marta Iruarrizaga-Lejarreta, Teresa C. Delgado, Marta Varela-Rey, Ana Senra, Vera Garcia-Outeiral, Eva Novoa, Cristina Iglesias, Begona Porteiro, Daniel Beiroa, Cintia Folgueira, Marta Tojo, Jorge L. Torres, Lourdes Hernandez-Cosido, Oscar Blanco, Juan Pablo Arab, Francisco Barrera, Diana Guallar, Miguel Fidalgo, Miguel Lopez, Carlos Dieguez, Miguel Marcos, Maria L. Martinez-Chantar, Marco Arrese, Carmelo Garcia-Monzon, Jose M. Mato, Patricia Aspichueta, Ruben Nogueiras
Summary: The LPI/GPR55 system activates ACC to affect lipid metabolism, playing a role in the development of NAFLD and NASH. Inhibition of GPR55 and ACCα can block the effects of LPI, which may be a potential new strategy for treating NAFLD and NASH.
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
Biochemistry & Molecular Biology
Hossein Ghanizadeh, Christopher E. Buddenhagen, Kerry C. Harrington, Andrew G. Griffiths, Zachary Ngow
Summary: Resistance to ACCase-inhibiting herbicide pinoxaden in a population of L. perenne is characterized by the concurrent action of cytochrome P-450 activity enhancement and a rare target-site mutation. The resistant population showed different levels of resistance to other herbicides but remained susceptible to clethodim.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2022)
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
Chemistry, Multidisciplinary
Bappa Maiti, Krishan Kumar, Subhasis Datta, Santanu Bhattacharya
Summary: The membrane formation and aggregation properties of α-tocopherol-based cationic gemini lipids were extensively studied with varying polymethylene spacer lengths and the presence of hydroxyl functionalities at the headgroup region. The interaction of these lipids with model phospholipids and plasmid DNA showed that the aggregation behavior is strongly influenced by the length of the spacer and the presence of hydroxyl groups. The study provided a detailed characterization of the membranes formed from these lipids and highlighted the importance of inserting -OH groups at the headgroup region.
Review
Nanoscience & Nanotechnology
Bappa Maiti, Santanu Bhattacharya
Summary: Natural lipid molecules play a vital role in life, mainly contributing hydrophobicity through alkyl chains. Steroids and isoprenoids are important natural lipid molecules. Synthetic functionalized liposomal nanoparticles can be used for delivering genetic materials.
WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Soma Roy, Nirmal Chakraborty, Bappa Maiti, Kalappa Muniyappa, Santanu Bhattacharya
Summary: We have investigated the stabilization of higher-order noncanonical G-quadruplex (G4) DNA structures in oncogene promoter regions using newly synthesized nitrogen-containing aromatics conjugated to xanthone moiety. These compounds showed enhanced stability of G4 DNA and selective cytotoxicity for cancer cells. Spectroscopic measurements and melting experiments verified the G4 stabilization effect. These compounds induced the formation of parallel G4 structures even in the absence of added salt. Polymerase stop assay demonstrated the stability of G4 structures in oncogene promoters and the inhibition of DNA synthesis by these compounds. Apoptosis-mediated cell death and cell-cycle arrest in the S phase were observed in cancer cells. Molecular dynamics simulation studies suggested a binding mode involving the stacking of the xanthone core on the G4 DNA plane.
Article
Chemistry, Multidisciplinary
Subhajit Bhunia, Armando Pena-Duarte, Huifang Li, Hong Li, Mohamed Fathi Sanad, Pranay Saha, Matthew A. . Addicoat, Kotaro Sasaki, T. Amanda Strom, Miguel Jose Yacaman, Carlos R. . Cabrera, Ram Seshadri, Santanu Bhattacharya, Jean-Luc Bredas, Luis Echegoyen
Summary: Designing N-coordinated porous single-atom catalysts (SACs) is a promising approach for enhanced energy conversion. This study reports two efficient SAC systems, Co@rhm-PorBTD and Co@sql-PorBTD, based on Co(II)-porphyrin/ [2,1,3]-benzothiadiazole (BTD) covalent organic frameworks (COFs), for O2 electrocatalysis. Experimental results show that these COFs outperform commercial Pt/C by a large margin. The design and electrochemical performance of these COFs offer a pyrolysis-free bottom-up approach that avoids creating random atomic sites or unpredictable structural features.
Article
Chemistry, Multidisciplinary
S. Umesh, S. Sarkar, S. Bera, P. Moitra, S. Bhattacharya
Summary: A new hydrogel was developed by mixing 5'-guanosine monophosphate disodium salt and 1,4,5,8-naphthalene tetracarboxylic acid tetra potassium salt. The hydrogel showed excellent stability and pH-responsive properties. It was used for the encapsulation and delivery of an anticancer drug, and demonstrated high drug loading capacity and controlled release capabilities. In vivo studies showed significant regression of tumor volume after administration of the drug-loaded hydrogel.
MATERIALS TODAY CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Soma Roy, Bappa Maiti, Nilanjan Banerjee, Mangesh H. Kaulage, Kalappa Muniyappa, Subhrangsu Chatterjee, Santanu Bhattacharya
Summary: Xanthone is a significant scaffold for designing cytotoxic agents against cancer cells by stabilizing G-quadruplex nucleic acids. We synthesized xanthone-based derivatives with various side-arm substituents that showed selectivity for G4 DNA over dsDNA, verified through biophysical experiments. These compounds exhibit end-stacking mode of binding with G4 DNA and induce conformational changes in flanking nucleotides, suggesting their potential as potent anti-cancer agents.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Soma Roy, Santanu Bhattacharya
Summary: The study investigates the interaction between flavonoids and RNA-DNA hybrid structures using computational methods. The presence of an -OH group on the ligand and the availability of a proper binding pocket in the macromolecule are the main factors influencing the binding preference. The findings provide insights for the design of noncanonical nucleic acid-targeted drug molecules.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Multidisciplinary
Ashraf Mohammed, M. Brett Waddell, Ieva Sutkeviciute, Adithi Danda, Steven J. Philips, Walter Lang, P. Jake Slavish, Sandra J. Kietlinska, Mangesh Kaulage, Das Sourav, Aseem Z. Ansari
Summary: Researchers have designed a synthetic genome reader/regulator (SynGR) to target and restore the expression of a specific gene in a genetic disorder. They found that certain ligands can activate gene transcription, while others cannot. In addition, blocking one specific ligand enhances the activity of all active gene regulators. These findings provide insights into the regulation of gene expression and have implications for the design of more effective gene regulators.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Dipen Biswakarma, Nilanjan Dey, Santanu Bhattacharya
Summary: In this study, a stable and soft nanocomposite hydrogel comprised of a pyrene-based chiral amphiphile with an amino acid (l-phenylalanine) core and oligo-oxyethylene hydrophilic chains and graphene oxide (GO) was developed. The nanocomposite hydrogel exhibited superior mechanical stiffness and thixotropic properties compared to the native hydrogels. It was also used for optical sensing of biogenic polyamine and removal of toxic organic dyes from aqueous media.
Article
Oncology
Jyotsna Bhat-Ambure, Pravin Ambure, Eva Serrano-Candelas, Cristina Galiana-Rosello, Ariadna Gil-Martinez, Mario Guerrero, Margarita Martin, Jorge Gonzalez-Garcia, Enrique Garcia-Espana, Rafael Gozalbes
Summary: This study developed a computational tool called "G4-QuadScreen" to identify multi-target directed ligands (MTDLs) against G-quadruplexes (G4s). Through virtual screening and experimental validation, three compounds with strong inhibitory effect on various human cancer cell lines were discovered, demonstrating the usefulness of the computational tool in accelerating the discovery of novel anticancer therapies.
Article
Chemistry, Multidisciplinary
Dipen Biswakarma, Nilanjan Dey, Santanu Bhattacharya
Summary: A pyrene-based fluorogenic amphiphilic probe (1) was synthesized to form an injectable hydrogel in water, which enables sustainable delivery of two anticancer drugs, DOX and MT, under thermoresponsive conditions. The drug-loaded hydrogel showed a substantial difference in release rates at 25 and 37 degrees C, with cumulative releases of approximately 80% and 70% for DOX and MT, respectively, over 72 hours. The release of drug molecules followed zero-order kinetics and non-Fickian diffusion pathways. The stability of the hydrogel against proteinase enzymes suggests its potential for targeted and sustainable drug release in vivo. As expected, DOX-loaded hydrogels exhibited higher efficacy in killing cancer cells compared to free DOX.
JOURNAL OF CHEMICAL SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Sayan Umesh, Sayan Bera, Santanu Bhattacharya
Summary: This study develops a chiral organogel with thermo-reversible properties, forming fibrillar networks and 2D sheets. Circular dichroism studies reveal aggregation-induced chirality with circularly polarized luminescence. The 2D sheets exhibit enhanced piezoelectric responses compared to those from the fibrillar network. Introducing an electron-deficient dopant molecule leads to a charge-transfer complex and modulates the piezoelectric response.
Article
Chemistry, Multidisciplinary
Shabari Dutta, Suman Kalyan Samanta, Santanu Bhattacharya
Summary: Phosphate based organic polymer networks (OPNs) were synthesized for dye sorption and heterogeneous catalysis. These OPNs selectively adsorb cationic dyes and allow the synthesis and stabilization of gold nanoparticles within the networks, demonstrating effective catalytic reduction reactions.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Subhajit Bhunia, Pranay Saha, Parikshit Moitra, Matthew A. Addicoat, Santanu Bhattacharya
Summary: Solid porous and crystalline covalent organic frameworks have high specific surface areas and functional pore walls, allowing adsorption of bioactive molecules. A perylene-based COF was developed as a reservoir for an anticancer drug and the intracellular release of the drug was achieved using serum albumin.