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JOURNAL ARTICLE
Matin Nuhamunada, Omkar S Mohite, Patrick V Phaneuf, Bernhard O Palsson, Tilmann Weber
Genome mining is revolutionizing natural products discovery efforts. The rapid increase in available genomes demands comprehensive computational platforms to effectively extract biosynthetic knowledge encoded across bacterial pangenomes. Here, we present BGCFlow, a novel systematic workflow integrating analytics for large-scale genome mining of bacterial pangenomes. BGCFlow incorporates several genome analytics and mining tools grouped into five common stages of analysis such as: (i) data selection, (ii) functional annotation, (iii) phylogenetic analysis, (iv) genome mining, and (v) comparative analysis...
April 30, 2024: Nucleic Acids Research
#2
JOURNAL ARTICLE
Philipp M Roessner, Isabelle Seufert, Vicente Chapaprieta, Ruparoshni Jayabalan, Hannah Briesch, Ramon Massoni-Badosa, Pavle Boskovic, Julian Beckendorff, Tobias Roider, Lavinia Arseni, Mariana Coelho, Supriya Chakraborty, Alicia Vaca, Mariela Sivina, Markus Muckenhuber, Sonia Rodriguez-Rodriguez, Alice Bonato, Sophie A Herbst, Marc Zapatka, Clare Sun, Helene Kretzmer, Thomas Naake, Peter-Martin Bruch, Felix Czernilofsky, Elisa Ten Hacken, Martin Schneider, Dominic Helm, Deyan Yordanov Yosifov, Joseph Kauer, Alexey V Danilov, Moritz Bewarder, Kristina Heyne, Christof Schneider, Stephan Stilgenbauer, Adrian Wiestner, Jan-Philipp Mallm, Jan A Burger, Dimitar G Efremov, Peter Lichter, Sascha Dietrich, José Ignacio Martín-Subero, Karsten Rippe, Martina Seiffert
The T-box transcription factor T-bet is known as a master regulator of T-cell response but its role in malignant B cells is not sufficiently explored. Here, we conducted single-cell resolved multi-omics analyses of malignant B cells from patients with chronic lymphocytic leukemia (CLL) and studied a CLL mouse model with genetic knockout of TBX21. We found that T-bet acts as a tumor suppressor in malignant B cells by decreasing their proliferation rate. NF-κB activity induced by inflammatory signals provided by the microenvironment, triggered T-bet expression which impacted on promoter proximal and distal chromatin co-accessibility and controlled a specific gene signature by mainly suppressing transcription...
April 29, 2024: Blood
#3
REVIEW
Sang-Woo Han, Hyung-Sik Won
Ribosomally synthesized and post-translationally modified peptides (RiPPs) represent a significant potential for novel therapeutic applications because of their bioactive properties, stability, and specificity. RiPPs are synthesized on ribosomes, followed by intricate post-translational modifications (PTMs), crucial for their diverse structures and functions. PTMs, such as cyclization, methylation, and proteolysis, play crucial roles in enhancing RiPP stability and bioactivity. Advances in synthetic biology and bioinformatics have significantly advanced the field, introducing new methods for RiPP production and engineering...
April 15, 2024: Biomolecules
#4
REVIEW
Lilly E Cheek, Wen Zhu
In recent years, the biological significance of ribosomally synthesized, post-translationally modified peptides (RiPPs) and the intriguing chemistry catalyzed by their tailoring enzymes has garnered significant attention. A subgroup of bacterial radical S-adenosylmethionine (rSAM) enzymes can activate C-H bonds in peptides, which leads to the production of a diverse range of RiPPs. The remarkable ability of these enzymes to facilitate various chemical processes, to generate and harbor high-energy radical species, and to accommodate large substrates with a high degree of flexibility is truly intriguing...
April 23, 2024: Archives of Biochemistry and Biophysics
#5
JOURNAL ARTICLE
Chengyou Shi, Varshal A Patel, Douglas A Mitchell, Huimin Zhao
The β-hemolytic factor streptolysin S (SLS) is an important linear azol(in)e-containing peptide (LAP) that contributes significantly to the virulence of Streptococcus pyogenes. Despite its discovery 85 years ago, SLS has evaded structural characterizing owing to its notoriously problematic physicochemical properties. Here, we report the discovery and characterization of a structurally analogous hemolytic peptide from Enterococcus caccae, termed enterolysin S (ELS). Through heterologous expression, site-directed mutagenesis, chemoselective modification, and high-resolution mass spectrometry, we found that ELS contains an intriguing contiguous octathiazole moiety...
April 22, 2024: Chembiochem: a European Journal of Chemical Biology
#6
JOURNAL ARTICLE
Brian Choi, Arthur Acuña, A James Link
The ribosomally synthesized and post-translationally modified peptide (RiPP) superfamily of natural products includes many examples of cyclic peptides with diverse macrocyclization chemistries. The graspetides, one family of macrocyclized RiPPs, harbor side chain-side chain ester or amide linkages. We recently reported the structure and biosynthesis of the graspetide pre-fuscimiditide, a 22-amino-acid (aa) peptide with two ester cross-links forming a stem-loop structure. These cross-links are introduced by a single graspetide synthetase, the ATP-grasp enzyme ThfB...
April 18, 2024: Journal of the American Chemical Society
#7
JOURNAL ARTICLE
Surmani Huidrom, Ng Ngashangva, Joshua Khumlianlal, Kongbrailatpam Chandradev Sharma, Pulok Kumar Mukherjee, Sarangthem Indira Devi
Lactiplantibacillus plantarum BRD3A was isolated from Atingba, a traditional fermented rice-based beverage of Manipur. Its genomic sequence has 13 contigs and its genome size is 3,320,817 bp with a guanine-cytosine (GC) ratio of 44.6%. It comprises 3185 genes including 3112 coding sequences (CDSs), 73 RNAs (including 66 tRNAs and others), and one clustered regularly interspaced short palindromic repeat (CRISPR) array. A comparative and phylogenetic analysis with the Lp. plantarum genome shows that this strain has close similarity with other Lp...
2024: Frontiers in Microbiology
#8
JOURNAL ARTICLE
Manuela Montoya-Giraldo, Kathryn R Piper, Odion O Ikhimiukor, Cooper J Park, Nicole A Caimi, Debbie C Buecher, Ernest W Valdez, Diana E Northup, Cheryl P Andam
Streptomyces are prolific producers of secondary metabolites from which many clinically useful compounds have been derived. They inhabit diverse habitats but have rarely been reported in vertebrates. Here, we aim to determine to what extent the ecological source (bat host species and cave sites) influence the genomic and biosynthetic diversity of Streptomyces bacteria. We analysed draft genomes of 132 Streptomyces isolates sampled from 11 species of insectivorous bats from six cave sites in Arizona and New Mexico, USA...
April 2024: Microbial Genomics
#9
JOURNAL ARTICLE
Desy Putri Handayani, Alim Isnansetyo, Indah Istiqomah
Pseudoalteromonas viridis strain BBR56 was isolated from seawater at Dutungan Island, South Sulawesi, Indonesia. Bacterial DNA was isolated using Promega Genomic DNA TM050. DNA purity and quantity were assessed using NanoDrop spectrophotometers and Qubit fluorometers. The DNA library and sequencing were prepared using Oxford Nanopore Technology GridION MinKNOW 20.06.9 with long read, direct, and comprehensive analysis. High accuracy base calling was assessed with Guppy version 4.0.11. Filtlong and NanoPlot were used for filtering and visualizing the FASTQ data...
April 13, 2024: BMC Genomics
#10
JOURNAL ARTICLE
Michelle W Katzow, Caren Steinway, Errica Capossela, Jack Chen, Victoria Chen, Talia Fenster, Nirupa Galagedera, Megan Hamill, Elaine Lin, Erica Mamauag, Shannon Moriarty, Shivany Pathania, Lyndsey Pliskin, Asher Ripp, Avy Ronay, Maria T Santiago, Margaret Yang, Sophia Jan
Objective: We aimed to (1) describe telemedicine utilization and usability during the first 6 weeks of the pandemic and (2) determine if usability varied by individual- or visit-level characteristics. Methods: We conducted a retrospective cohort study of ambulatory pediatric telemedicine visits occurring between March 10, 2020, and April 18, 2020, across a large academic health system. We performed manual chart review to assess individual- and visit-level characteristics and invited caregivers to respond to an adapted Telehealth Usability Questionnaire (TUQ)...
April 9, 2024: Telemedicine Journal and E-health
#11
JOURNAL ARTICLE
Richard J Gilbertson, Sam Behjati, Anna-Lisa Böttcher, Marianne E Bronner, Matthew Burridge, Henrick Clausing, Harry Clifford, Tracey Danaher, Laura K Donovan, Jarno Drost, Alexander M M Eggermont, Chris Emerson, Mona G Flores, Petra Hamerlik, Nada Jabado, Andrew Jones, Henrick Kaessmann, Claudia L Kleinman, Marcel Kool, Lena M Kutscher, Gavin Lindberg, Emily Linnane, John C Marioni, John M Maris, Michelle Monje, Alexandra Macaskill, Steven Niederer, Paul A Northcott, Elizabeth Peeters, Willemijn Plieger-van Solkema, Liane Preußner, Anne C Rios, Karsten Rippe, Peter Sandford, Nikolaos G Sgourakis, Adam Shlien, Pete Smith, Karin Straathof, Patrick J Sullivan, Mario L Suvà, Michael D Taylor, Emma Thompson, Roser Vento-Tormo, Brandon J Wainwright, Robert J Wechsler-Reya, Frank Westermann, Shannon Winslade, Bissan Al-Lazikani, Stefan M Pfister
We are building the world's first Virtual Child-a computer model of normal and cancerous human development at the level of each individual cell. The Virtual Child will "develop cancer" that we will subject to unlimited virtual clinical trials that pinpoint, predict, and prioritize potential new treatments, bringing forward the day when no child dies of cancer, giving each one the opportunity to lead a full and healthy life.
April 4, 2024: Cancer Discovery
#12
JOURNAL ARTICLE
Prabin Tamang, Arjun Upadhaya, Pradeep Paudel, Kumudini Meepagala, Charles L Cantrell
Natural product (NP)-based pesticides have emerged as a compelling alternative to traditional chemical fungicides, attracting substantial attention within the agrochemical industry as the world is pushing toward sustainable and environmentally friendly approaches to safeguard crops. Microbes, both bacteria and fungi, are a huge source of diverse secondary metabolites with versatile applications across pharmaceuticals, agriculture, and the food industry. Microbial genome mining has been accelerated for pesticide/drug discovery and development in recent years, driven by advancements in genome sequencing, bioinformatics, metabolomics/metabologenomics, and synthetic biology...
March 9, 2024: Microorganisms
#13
JOURNAL ARTICLE
Hengqian Ren, Chunshuai Huang, Yuwei Pan, Shravan R Dommaraju, Haiyang Cui, Maolin Li, Mayuresh G Gadgil, Douglas A Mitchell, Huimin Zhao
Recent efforts in genome mining of ribosomally synthesized and post-translationally modified peptides (RiPPs) have expanded the diversity of post-translational modification chemistries. However, RiPPs are rarely reported as hybrid molecules incorporating biosynthetic machinery from other natural product families. Here we report lipoavitides, a class of RiPP/fatty-acid hybrid lipopeptides that display a unique, putatively membrane-targeting 4-hydroxy-2,4-dimethylpentanoyl (HMP)-modified N terminus. The HMP is formed via condensation of isobutyryl-coenzyme A (isobutyryl-CoA) and methylmalonyl-CoA catalysed by a 3-ketoacyl-(acyl carrier protein) synthase III enzyme, followed by successive tailoring reactions in the fatty acid biosynthetic pathway...
March 25, 2024: Nature Chemistry
#14
JOURNAL ARTICLE
Botao Cheng, Yanqing Xue, Yuting Duan, Wen Liu
The carboxyl-terminal (C-terminal) S-[(Z)-2-aminovinyl]-cysteine (AviCys) analogs have been identified in four families of ribosomally synthesized and post-translationally modified peptides (RiPPs): lanthipeptides, linaridins, thioamitides, and lipolanthines. Within identified biosynthetic pathways, a highly reactive enethiol intermediate, formed through an oxidative decarboxylation catalyzed by a LanD-like flavoprotein, can undergo two types of cyclization: a Michael addition with a dehydroamino acid or a coupling reaction initiated by a radical species...
February 27, 2024: ChemPlusChem
#15
JOURNAL ARTICLE
Mushineni Ashajyothi, Shivannegowda Mahadevakumar, Y N Venkatesh, Pullabhotla V S R N Sarma, Chalasani Danteswari, Alexander Balamurugan, Ganesan Prakash, Vikas Khandelwal, C Tarasatyavathi, Appa Rao Podile, Mysore S Kirankumar, Siddaiah Chandranayaka
BACKGROUND: Plant microbiome confers versatile functional roles to enhance survival fitness as well as productivity. In the present study two pearl millet panicle microbiome member species Bacillus subtilis PBs 12 and Bacillus paralicheniformis PBl 36 found to have beneficial traits including plant growth promotion and broad-spectrum antifungal activity towards taxonomically diverse plant pathogens. Understanding the genomes will assist in devising a bioformulation for crop protection while exploiting their beneficial functional roles...
March 18, 2024: BMC Plant Biology
#16
JOURNAL ARTICLE
Lonnie A Harris, Hamada Saad, Kyle E Shelton, Lingyang Zhu, Xiaorui Guo, Douglas A Mitchell
Lasso peptides are a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) defined by a macrolactam linkage between the N-terminus and the side chain of an internal aspartic acid or glutamic acid residue. Instead of adopting a branched-cyclic conformation, lasso peptides are "threaded", with the C-terminal tail passing through the macrocycle to present a kinetically trapped rotaxane conformation. The availability of enhanced bioinformatics methods has led to a significant increase in the number of secondary modifications found on lasso peptides...
March 18, 2024: Biochemistry
#17
JOURNAL ARTICLE
Joel P Bercu, David J Ponting, Sharon L Ripp, Krista L Dobo, Rheem A Totah, Jayaprakasam Bolleddula
No abstract text is available yet for this article.
March 18, 2024: Clinical Pharmacology and Therapeutics
#18
JOURNAL ARTICLE
Rabeb Teber, Shuichi Asakawa
Due to their potential application as an alternative to antibiotics, bacteriocins, which are ribosomally synthesized antimicrobial peptides produced by bacteria, have received much attention in recent years. To identify bacteriocins within marine bacteria, most of the studies employed a culture-based method, which is more time-consuming than the in silico approach. For that, the aim of this study was to identify potential bacteriocin gene clusters and their potential producers in 51 marine Bacillota (formerly Firmicutes ) genomes, using BAGEL4, a bacteriocin genome mining tool...
February 22, 2024: International Journal of Molecular Sciences
#19
Joseph D Clark, Xuenan Mi, Douglas A Mitchell, Diwakar Shukla
Ribosomally synthesized and post-translationally modified peptide (RiPP) biosynthetic enzymes often exhibit promiscuous substrate preferences that cannot be reduced to simple rules. Large language models are promising tools for predicting such peptide fitness landscapes. However, state-of-the-art protein language models are trained on relatively few peptide sequences. A previous study comprehensively profiled the peptide substrate preferences of LazBF (a two-component serine dehydratase) and LazDEF (a three-component azole synthetase) from the lactazole biosynthetic pathway...
February 23, 2024: ArXiv
#20
JOURNAL ARTICLE
Pablo Machado Soares, Amanda Maria de Oliveira Dal Piva, Gabriel Kalil Rocha Pereira, Luiz Felipe Valandro, Marilia Pivetta Rippe, Albert J Feilzer, Cornelis Johannes Kleverlaan, João Paulo Mendes Tribst
OBJECTIVE: The aim of the present study was to evaluate the influence of multidirectional brushing on the surface roughness, morphology, and bonding interface of resin-repaired CAD-CAM ceramic and composite restorations. MATERIALS AND METHODS: Twelve (N = 12) blocks (4 mm × 4 mm × 2 mm for parallel axis; 5 mm × 4 mm × 2 mm for perpendicular axis) of lithium disilicate glass-ceramic (IPS e.max CAD, Ivoclar AG) and CAD-CAM resin composite (Tetric CAD, Ivoclar AG) were obtained and repaired with direct resin composite (Clearfil AP-X, Kuraray)...
March 8, 2024: International Dental Journal
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