SECRETed_8th_Newsletter

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Grant Agreement No 101000794. Newsletter Magazine 8th Issue May 2025 In this Issue 1. SECRETed Overview 2.RecentPublications 3.Events&KeyActivities 4. Recent Partners' Achievements 5.StayConnected TogainaccesstoourforthcomingNewsletterssubscribethroughourwebsite. CheckthepreviousissuesofNewsletterHERE COPYRIGHT© 2 Whatwedo SECRETed is an innovative EU-funded research project aiming to unlock the potential of nature’s microorganisms. It achieves this by combining multiple scientific disciplines such as biology, biotechnology, artificial intelligence, and industrial production to discover natural ingredients and develop new ones with custom properties. These ingredients enhance the effectiveness of a wide range of products used in applications such as pharmaceuticals, cosmetics, food supplements, and agriculture. SECRETed Overview • More effective treatment of chronic diseases • Tackling antibiotic-resistant microbes • Anti-aging and anti-wrinkle formulations • Early detection and treatment of inflammatory diseases • More efficient use of fertilisers SECRETed focuses on biosurfactants and siderophores, which have the ability to protect and support the function of active ingredients, such as antioxidants and fertilisers, during their application and absorption by the human body or plants, respectively. Biosurfactants: Substances that allow fluids (like water) to “capture” and dissolve other desired or undesired substances, such as impurities, antioxidants, oils, etc. Siderophores: Molecules used by microorganisms to “bind” the iron in their environment. Iron is a critical element for microbial growth, as it is in humans, where it plays a vital role in oxygen transport. 3 The production of bioactive chemicals hasnotbeenthoroughlymappedorstudiedforthousandsofmicroorganisms existing in aquatic or extreme environments. SECRETed addresses more than 5,000 microorganisms, which have been systematically screened for the bioproduction of biosurfactants and siderophores with industry-driven properties. Howwedoit 1. SECRETed rapidly and efficiently screens thousands of microorganisms using Artificial Intelligence tools and experimental data to identify those producing high-interest biosurfactant and siderophore compounds. 2. The DNA of selected microorganisms is mapped to identify genes and functions responsible for synthesising specialty chemicals. 3. Biotechnology techniques are applied for natural or modified microorganisms to produce enhanced chemical compounds with specific properties. 4. The cultivation of these microorganisms is scaled up to pilot-scale production. 5. Chemical compounds are tested and optimised in real-life applications, such as: • Formulations with anti-tumoral activity as well as treatments for eye diseases (e.g., glaucoma, cataract, macular degeneration) • New antibiotics to combat bacteria resistant to current treatments • High-efficiency antioxidant formulations with anti-aging and anti-wrinkle effects • Novel methods for early detection and treatment of inflammatory diseases • Protection of fertilizers from adverse weather conditions (e.g., rain) and controlled release. SECRETed Overview SECRETedFunctions • Microbial collections screening • Databases integration • Systems metabolic engineering • Lab-scale fermentation & characterisation • Pilot process optimisation • End users’ applications • Sustainability assessment 4 Production and extraction of surfactants and siderophores from selected halophilic bacteria has been performed ( University of Seville ). The extracts were analysed by StazioneZoologicaAnton Dohrn (Italy), and the compounds were tested in final applications. With the help of bioinformatics ( IDENERR&D , Spain), genes were identified, and novel gene combinations were investigated to produce biosurfactants with desirable properties. The University of Athens , in collaboration with PharmaMar (Spain), successfully identified and characterised siderophores and bioactive compounds with potential anti-cancer properties. Specific compounds were selected for further analysis and development of pharmaceuticals. SECRETed Overview What has been achieved Successful pilot-scale testing of SECRETed technologies has been achieved by BioBaseEuropePilotPlant (Belgium). Sphera Encapsulation (Italy) developed enhanced emulsifying biosurfactants for efficient fertilizers and food supplements using essential oils (oregano) and bioactive ingredients (Coenzyme Q10), respectively. AccuplexDiagnostics (Ireland) developed new siderophore compounds that reduces, or even ceases, the growth of two antibiotic-resistant bacteria, Klebsiella pneumoniae and Acinetobacter baumannii, which are responsible for a wide range of infections such as pneumonia, urinary tract infection, sepsis, diarrhea, and skin infections. AccuplexDiagnostics also released the rapid test SideroTecHiSen™ , which detects inflammation-causing microbes with sensitivity up to 100 times greater than other methods, in just 10 minutes without the need for culturing. 5 Abstract Microbial biosurfactants have garnered significant interest from industry due to their lower toxicity, biodegradability, activity at lower concentrations and higher resistance compared to synthetic surfactants. The deep-sea Rhodococcus sp. I2R has been identified as a producer of glycolipid biosurfactants, specifically succinoyl trehalolipids, which exhibit antiviral activity. However, genome mining of this bacterium has revealed a still unexplored repertoire of biosurfactants. The microbial genome was found to host five non-ribosomal peptide synthetase (NRPS) gene clusters containing starter condensation domains that direct lipopeptide biosynthesis. Genomics and mass spectrometry (MS)-based metabolomics enabled the linking of two NRPS gene clusters to the corresponding lipopeptide families, leading to the identification of 20 new cyclolipopeptides, designated as rhodoheptins, and 33 new glycolipopeptides, designated as rhodamides. An integrated in silico gene cluster and high-resolution MS/MS data analysis allowed us to elucidate the planar structure, inference of stereochemistry and reconstruction of the biosynthesis of rhodoheptins and rhodamides. Rhodoheptins are cyclic heptapeptides where the N-terminus is bonded to a β-hydroxy fatty acid forming a macrolactone ring with the C-terminal amino acid residue. Rhodamides are linear 14-mer glycolipopeptides with a serine-and alanine-rich peptide backbone, featuring a distinctive pattern of acetylation, glycosylation and succinylation. These molecules exhibited biosurfactant activity in the oilspreading assay and showed moderate antiproliferative effects against human A375 melanoma cells. 24 November 2024 | https://doi.org/10.1111/1751-7915.70011 Recent Publications Integratedgenomeandmetabolome miningunveiledstructureandbiosynthesis ofnovellipopeptidesfromadeep-sea Rhodococcus 6 Abstract With rising concerns about antimicrobial resistance, the identification of new lead compounds to target multidrug-resistant bacteria is essential. This study employed a fast miniaturised screening to simultaneously cultivate and evaluate about 300 marine strains for biosurfactant and antibacterial activities, leading to the selection of the deepsea Bacillus halotolerans BCP32. The integration of tandem mass spectrometry molecular networking and bioassay-guided fractionation unveiled this strain as a prolific factory of surfactins and nobilamides. Particularly, 84 nobilamide congeners were identified in the bacterial exometabolome, 71 of them being novel metabolites. Among these, four major compounds were isolated, including the known TL-119 and nobilamide I, as well as the two new nobilamides T1 and S1. TL-119 and nobilamide S1 exhibited potent antibiotic activity against various multidrug-resistant Staphylococcus strains and other Gram-positive pathogens, including the foodborne pathogen Listeria monocytogenes. Finally, in silico analysis of Bacillus halotolerans BCP32 genome revealed nobilamide biosynthesis to be directed by a previously unknown heptamodular nonribosomal peptide synthetase. Mar. Drugs 2025, 23(1), 41 | https://doi.org/10.3390/ md23010041 NovelInsightsintotheNobilamideFamily fromaDeep-SeaBacillus:Chemical Diversity,BiosynthesisandAntimicrobial ActivityTowardsMultidrug-Resistant Bacteria Recent Publications 7 Abstract Specialised or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardised and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015. Since its conception, MIBiG has been regularly updated to expand data coverage and remain up to date with innovations in natural product research. Here, we describe MIBiG version 4.0, an extensive update to the data repository and the underlying data standard. In a massive community annotation effort, 267 contributors performed 8304 edits, creating 557 new entries and modifying 590 existing entries, resulting in a new total of 3059 curated entries in MIBiG. Particular attention was paid to ensuring high data quality, with automated data validation using a newly developed custom submission portal prototype, paired with a novel peer-revie wing model. MIBiG 4.0 also takes steps towards a rolling release model and a broader involvement of the scientific community. MIBiG 4.0 is accessible online at https:// mibig.secondarymetabolites.org/. Nucleic Acids Research, Volume 53, Issue D1, 6 January 2025, Pages D678–D690 | https://doi.org/10.1093/ nar/gkae1115 MIBiG4.0:advancingbiosynthetic geneclustercurationthroughglobal collaboration Recent Publications 8 FullListofPublications Publications TITLEOFTHESCIENTIFICPUBLICATIONS 1Combining OSMAC Approach and Untargeted Metabolomics for the Identification of New Glycolipids with Potent Antiviral Activity Produced by a Marine Rhodococcus 2Antiviral Activity of the Rhamnolipids Mixture from the Antarctic Bacterium Pseudomonas gessardii M15 against Herpes Simplex Viruses and Coronaviruses 3Applicability of Control Materials To Support Gene Promoter Characterization and Expression in Engineered Cells Using Digital PCR 4Novel Insights on Pyoverdine: From Biosynthesis to Biotechnological Application 5Medium development and production of carotenoids and exopolysaccharides by the extremophile Rhodothermus marinus DSM16675 in glucose-based defined media 6Dihydroauroglaucin Isolated from the Mediterranean Sponge Grantia compressa Endophyte Marine Fungus Eurotium chevalieri Inhibits Migration of Human Neuroblastoma Cells 7MIBiG 3.0: a community-driven effort to annotate experimentally validated biosynthetic gene clusters 8Production of selenium nanoparticles occurs through an interconnected pathway of sulphur metabolism and oxidative stress response in Pseudomonas putida KT2440 9Water potential governs the effector specificity of the transcriptional regulator XylR of Pseudomonas putida 10 Evaluation of Antimicrobial Properties and Potential Applications of Pseudomonas gessardii M15 Rhamnolipids towards Multiresistant Staphylococcus aureus 11 Prolonged Subculturing of Aspergillus fumigatus on Galleria Extract Agar Results in Altered Virulence and Sensitivity to Antifungal Agents 12 New Imidazolium Alkaloids with Broad Spectrum of Action from the Marine Bacterium Shewanella aquimarina 13 Gliotoxin-mediated bacterial growth inhibition is caused by specific metal ion depletion 9 7thAnnualGeneralMeetingofSECRETed,January9-10,2025 The 7th General Assembly meeting was held in Seville and was dedicated to a detailed presentation of work progress by all project entities, and planning of next actions. SECRETed featured extensive progress and achievements across all work packages. MicrobiologySocietyAnnualMeeting,November5-6,2024 Accuplex Diagnostics attended the Microbiology Society Annual Meeting disseminating the end-user applications of SECRETed project. Events & Key Activities SECRETedΕvents 3rdannualAIMSClustermeeting,February25,2025 The 3rd annual meeting of A.I.M.S. Cluster was held virtually and offered a valuable opportunity for all 4 founding projects – InnCoCells , Algae4IBD , SECRETed , MARBLES – to discuss about their latest research advancements, common challenges and strategies to overcome them, as well as to plan their future joint activities. FreeSECRETedWebinar,January20,2025 The event featured 12 insightful presentations from SECRETed members and 1 Invited Speaker: Dr. Olga Genilloud, Fundación MEDINA (Spain). The online event attracted significant interest, with 91 attendees from 78 different entities and organisations, highlighting the significance and broad scientific impact of the project’s results across multiple domains. The webinar provided an open platform for attendees to engage directly with the speakers through two Q&A sessions. A Certificate of Attendance was also served to attendees. 9 16 Contact Info @SECRETedProjectH2020 @SECRETedProject @SecretedH www.secreted.eu/ ProjectCoordinator IDENERRESEARCH&DEVELOPMENT AGRUPACIONDEINTERESECONOMICO Calle Early Ovington 24-8, La Rinconada Sevilla, 41300, ES [email protected] SubscribetoourNEWSLETTER SustainableExploitationofbio-basedCompounds RevealedandEngineeredfromnaTuralsources TheSECRETedconsortium This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Grant Agreement No 101000794. 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