1. Oxytetracycline hyper-production through targeted genome reduction of Streptomyces rimosusAlen Pšeničnik, Lucija Slemc, Martina Avbelj, Miha Tome, Martin Šala, Paul R. Herron, Maksym Shmatkov, Marko Petek, Špela Baebler, Peter Mrak, Daslav Hranueli, Antonio Starcevic, Iain S. Hunter, Hrvoje Petković, 2024, original scientific article Abstract: Most biosynthetic gene clusters (BGC) encoding the synthesis of important microbial secondary metabolites, such as antibiotics, are either silent or poorly expressed; therefore, to ensure a strong pipeline of novel antibiotics, there is a need to develop rapid and efficient strain development approaches. This study uses comparative genome analysis to instruct rational strain improvement, using Streptomyces rimosus, the producer of the important antibiotic oxytetracycline (OTC) as a model system. Sequencing of the genomes of two industrial strains M4018 and R6-500, developed independently from a common ancestor, identified large DNA rearrangements located at the chromosome end. We evaluated the effect of these genome deletions on the parental S. rimosus Type Strain (ATCC 10970) genome where introduction of a 145 kb deletion close to the OTC BGC in the Type Strain resulted in massive OTC overproduction, achieving titers that were equivalent to M4018 and R6-500. Transcriptome data supported the hypothesis that the reason for such an increase in OTC biosynthesis was due to enhanced transcription of the OTC BGC and not due to enhanced substrate supply. We also observed changes in the expression of other cryptic BGCs; some metabolites, undetectable in ATCC 10970, were now produced at high titers. This study demonstrated for the first time that the main force behind BGC overexpression is genome rearrangement. This new approach demonstrates great potential to activate cryptic gene clusters of yet unexplored natural products of medical and industrial value.
Keywords: genome reduction, antibiotic biosynthesis, oxytetracycline, cryptic metabolites
Published in DiRROS: 07.08.2024; Views: 83; Downloads: 110
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2. Adjusting the operational potential window as a tool for prolonging the durability of carbon-supported Pt-alloy nanoparticles as oxygen reduction reaction electrocatalystsTina Đukić, Leonard Moriau, Iva Klofutar, Martin Šala, Luka Pavko, Francisco Javier Gonzalez Lopez, Francisco Ruiz-Zepeda, Andraž Pavlišič, Miha Hotko, Matija Gatalo, Nejc Hodnik, 2024, original scientific article Published in DiRROS: 05.08.2024; Views: 122; Downloads: 96
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3. Quantitative insights on impurities in ice cores at the micro-scale from calibrated LA-ICP-MS imagingPascal Bohleber, Piers Larkman, Nicolas Stoll, David Clases, Raquel Gonzalez de Vega, Martin Šala, Marco Roman, Carlo Barbante, 2024, original scientific article Published in DiRROS: 10.06.2024; Views: 196; Downloads: 169
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4. Towards improved online dissolution evaluation of Pt-alloy PEMFC electrocatalysts via electrochemical flow cell - ICP-MS setup upgradesLeonard Moriau, Tina Đukić, Vojtech Domin, Roman Kodym, Martin Prokop, Karel Bouzek, Matija Gatalo, Martin Šala, Nejc Hodnik, 2024, original scientific article Published in DiRROS: 29.04.2024; Views: 315; Downloads: 253
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6. Evaluation of two-phase sample transport upon ablation of gelatin as a proxy for soft biological matrices using nanosecond laser ablation – inductively coupled plasma – mass spectrometryTom Van Helden, Kristina Mervič, Ivan Nemet, Johannes Teun van Elteren, Frank Vanhaecke, Sanda Rončević, Martin Šala, Thibaut Van Acker, 2024, original scientific article Published in DiRROS: 27.02.2024; Views: 374; Downloads: 221
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10. Periodic anti-phase boundaries and crystal superstructures in ▫$PtCu_3$▫ nanoparticles as fuel cell electrocatalystsAna Rebeka Kamšek, Anton Meden, Iztok Arčon, Primož Jovanovič, Martin Šala, Francisco Ruiz-Zepeda, Goran Dražić, Miran Gaberšček, Marjan Bele, Nejc Hodnik, 2023, original scientific article Published in DiRROS: 28.08.2023; Views: 670; Downloads: 314
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