{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T13:42:56Z","timestamp":1760708576524,"version":"build-2065373602"},"reference-count":55,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>The marine invertebrate-associated microbiome has garnered significant interest in recent years due to its wealth of novel genes that can be explored for biomining. By combining genomics with untargeted data-dependent mass spectrometry (MS) and molecular networking, we characterized the secreted metabolome of Streptomyces sp. In a previous study, we isolated and characterized a strain of Streptomyces, designated as strain 34, from the nudibranch Chromodoris quadricolor, collected by SCUBA diving in the Red Sea near El Tor in the Gulf of Suez, Egypt. In the present study, the Streptomyces isolate was identified as Streptomyces tunisiensis GCF 039538125 1 (p-value: 0). Genomic and metabolomic analysis reveal 36 predicted biosynthetic gene clusters. A total of 569 metabolites were detected in the culture, with 86 of these being identified based on standards and public spectral libraries. Moreover, a single lassopeptide synthesis gene cluster was found in both the genome and the metabolic extract, along with various sets of siderophores identified in the metabolic extract. Since the metabolic processes of marine invertebrate microbiomes are poorly understood, our findings are a significant addition to the research on metabolism in host microbiomes.<\/jats:p>","DOI":"10.3390\/md23100404","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T13:07:22Z","timestamp":1760706442000},"page":"404","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genomic and Metabolomic Insights into Metabolites of a Streptomyces Isolate Associated with Chromodoris quadricolor, a Red Sea Nudibranch"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5586-2033","authenticated-orcid":false,"given":"Samar M.","family":"Abdelrahman","sequence":"first","affiliation":[{"name":"School of Earth and Atmospheric Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA"},{"name":"Department of Botany and Microbiology, Faculty of Science, Suez University, Suez 43221, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zoe A.","family":"Pratte","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA"},{"name":"Department of Microbiology & Immunology, Montana State University, Bozeman, MT 59717, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manar","family":"El Samak","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, Faculty of Pharmacy, Suez Canal University, Ismailia 43518, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4434-9146","authenticated-orcid":false,"given":"Noura S.","family":"Dosoky","sequence":"additional","affiliation":[{"name":"Salt Lake Community College, Salt Lake City, UT 84123, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4937-7741","authenticated-orcid":false,"given":"Amro M. S.","family":"Hanora","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, Faculty of Pharmacy, Suez Canal University, Ismailia 43518, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank J.","family":"Stewart","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA"},{"name":"Department of Microbiology & Immunology, Montana State University, Bozeman, MT 59717, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole B.","family":"Lopanik","sequence":"additional","affiliation":[{"name":"School of Earth and Atmospheric Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA"},{"name":"School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA"},{"name":"American Cancer Society, Atlanta, GA 30303, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.1021\/acs.jnatprod.7b00560","article-title":"Thermoactinoamide A, an Antibiotic Lipophilic Cyclopeptide from the Icelandic Thermophilic Bacterium Thermoactinomyces vulgaris","volume":"80","author":"Teta","year":"2017","journal-title":"J. Nat. Prod."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41573-020-00114-z","article-title":"Natural products in drug discovery: Advances and opportunities","volume":"20","author":"Atanasov","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/j.chom.2024.05.015","article-title":"Antibiotic resistance: A key microbial survival mechanism that threatens public health","volume":"32","author":"Abbas","year":"2024","journal-title":"Cell Host Microbe"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"100081","DOI":"10.1016\/j.glmedi.2024.100081","article-title":"Antimicrobial resistance: Impacts, challenges, and future prospects","volume":"2","author":"Ahmed","year":"2024","journal-title":"J. Med. Surg. Public Health"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ahmed, I., Asgher, M., Sher, F., Hussain, S.M., Nazish, N., Joshi, N., Sharma, A., Parra-Sald\u00edvar, R., Bilal, M., and Iqbal, H.M.N. (2022). Exploring Marine as a Rich Source of Bioactive Peptides: Challenges and Opportunities from Marine Pharmacology. Mar. Drugs, 20.","DOI":"10.3390\/md20030208"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1039\/C7NP00052A","article-title":"Marine natural products","volume":"35","author":"Blunt","year":"2018","journal-title":"Nat. Prod. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/978-3-540-30880-5_8","article-title":"Chemical diversity in opisthobranch molluscs from scarcely investigated Indo-Pacific areas","volume":"43","author":"Wahidullah","year":"2006","journal-title":"Prog. Mol. Subcell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1039\/C7NP00041C","article-title":"The chemistry and chemical ecology of nudibranchs","volume":"34","author":"Dean","year":"2017","journal-title":"Nat. Prod. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Scheuer, P.J. (1987). Bioorganic Marine Chemistry, Berlin, Heidelberg, 1987. Chemical Ecology of the Nudibranchs, Springer.","DOI":"10.1007\/978-3-642-72726-9"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e10525","DOI":"10.7717\/peerj.10525","article-title":"The natural product biosynthetic potential of Red Sea nudibranch microbiomes","volume":"9","author":"Abdelrahman","year":"2021","journal-title":"PeerJ"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Nguyen, C.T., Dhakal, D., Pham, V.T.T., Nguyen, H.T., and Sohng, J.-K. (2020). Recent Advances in Strategies for Activation and Discovery\/Characterization of Cryptic Biosynthetic Gene Clusters in Streptomyces. Microorganisms, 8.","DOI":"10.3390\/microorganisms8040616"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Sharma, V., Kaur, R., and Salwan, R. (2021). Streptomyces: Host for refactoring of diverse bioactive secondary metabolites. 3 Biotech, 11.","DOI":"10.1007\/s13205-021-02872-y"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Sarmiento-Tovar, A.A., Silva, L., S\u00e1nchez-Su\u00e1rez, J., and Diaz, L. (2022). Streptomyces-Derived Bioactive Pigments: Ecofriendly Source of Bioactive Compounds. Coatings, 12.","DOI":"10.3390\/coatings12121858"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Alam, K., Mazumder, A., Sikdar, S., Zhao, Y.M., Hao, J., Song, C., Wang, Y., Sarkar, R., Islam, S., and Zhang, Y. (2022). Streptomyces: The biofactory of secondary metabolites. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.968053"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Enany, S. (2018). Streptomyces Secondary Metabolites. Basic Biology and Applications of Actinobacteria, IntechOpen.","DOI":"10.5772\/intechopen.72033"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Klebe, G. (2024). Screening Technologies for Lead Structure Discovery. Drug Design: From Structure and Mode-of-Action to Rational Design Concepts, Springer.","DOI":"10.1007\/978-3-662-68998-1"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1177\/2472630318817735","article-title":"The Complexity of Compliance in Sample Management: A Review of Key Issues Impacting Small-Molecule and Biological Sample Management in Early Drug Discovery","volume":"24","author":"Crimmin","year":"2019","journal-title":"SLAS Technol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.phytol.2016.11.006","article-title":"Strategies for dereplication of natural compounds using high-resolution tandem mass spectrometry","volume":"21","author":"Kind","year":"2017","journal-title":"Phytochem. Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/nchembio.2219","article-title":"Dereplication of peptidic natural products through database search of mass spectra","volume":"13","author":"Mohimani","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4035","DOI":"10.1038\/s41467-018-06082-8","article-title":"Dereplication of microbial metabolites through database search of mass spectra","volume":"9","author":"Mohimani","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1099\/mic.0.000386","article-title":"Sequencing rare marine actinomycete genomes reveals high density of unique natural product biosynthetic gene clusters","volume":"162","author":"Schorn","year":"2016","journal-title":"Microbiology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1039\/C8NP00092A","article-title":"Marine natural products","volume":"36","author":"Carroll","year":"2019","journal-title":"Nat. Prod. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11959","DOI":"10.1021\/acs.analchem.2c02245","article-title":"Integrated Metabolomic-Genomic Workflows Accelerate Microbial Natural Product Discovery","volume":"94","author":"Avalon","year":"2022","journal-title":"Anal. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Abdelrahman, S.M., Dosoky, N.S., Hanora, A.M., and Lopanik, N.B. (2022). Metabolomic Profiling and Molecular Networking of Nudibranch-Associated Streptomyces sp. SCSIO 001680. Molecules, 27.","DOI":"10.3390\/molecules27144542"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s10482-013-0086-z","article-title":"Streptomyces tunisiensis sp. nov. a novel Streptomyces species with antibacterial activity","volume":"105","author":"Slama","year":"2014","journal-title":"Antonie Van Leeuwenhoek"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s12934-023-02106-1","article-title":"Exploring the antimicrobial, antiviral, antioxidant, and antitumor potentials of marine Streptomyces tunisiensis W4MT573222 pigment isolated from Abu-Qir sediments, Egypt","volume":"22","author":"Ibrahim","year":"2023","journal-title":"Microb. Cell Factories"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Slama, N., Mankai, H., and Limam, F. (2021). Streptomyces tunisiensis DSM 42037 mediated bioconversion of ferulic acid released from barley bran. World J. Microbiol. Biotechnol., 37.","DOI":"10.1007\/s11274-021-03031-4"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"W448","DOI":"10.1093\/nar\/gkt391","article-title":"BAGEL3: Automated identification of genes encoding bacteriocins and (non-)bactericidal posttranslationally modified peptides","volume":"41","author":"Heel","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1038\/sj.bjc.6690451","article-title":"Mode of action of thiocoraline, a natural marine compound with anti-tumour activity","volume":"80","author":"Erba","year":"1999","journal-title":"Br. J. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1002\/emmm.201201689","article-title":"Towards a new tuberculosis drug: Pyridomycin\u2014nature\u2019s isoniazid","volume":"4","author":"Hartkoorn","year":"2012","journal-title":"EMBO Mol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8894","DOI":"10.1002\/chem.201901640","article-title":"Synthesis of New Cyclomarin Derivatives and Their Biological Evaluation towards Mycobacterium Tuberculosis and Plasmodium Falciparum","volume":"25","author":"Kiefer","year":"2019","journal-title":"Chemistry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1021\/ol303374e","article-title":"Chlorizidine, a cytotoxic 5H-pyrrolo[2,1-a]isoindol-5-one-containing alkaloid from a marine Streptomyces sp","volume":"15","author":"Jensen","year":"2013","journal-title":"Org. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"123","DOI":"10.7164\/antibiotics.51.123","article-title":"Cremimycin, a novel 19-membered macrocyclic lactam antibiotic, from Streptomyces sp","volume":"51","author":"Igarashi","year":"1998","journal-title":"J. Antibiot."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1038\/nbt.3597","article-title":"Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking","volume":"34","author":"Wang","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.7164\/antibiotics.40.1664","article-title":"Bisucaberin, a new siderophore, sensitizing tumor cells to macrophage-mediated cytolysis. I. Taxonomy of the producing organism, isolation and biological properties","volume":"40","author":"Kameyama","year":"1987","journal-title":"J. Antibiot."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1021\/ja00032a043","article-title":"Solution thermodynamics of the ferric complexes of new desferrioxamine siderophores obtained by directed fermentation","volume":"114","author":"Jung","year":"1992","journal-title":"J. Am. Chem. Soc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/BF00173718","article-title":"Production of desferrioxamine E and new analogues by directed fermentation and feeding fermentation","volume":"32","author":"Meiwes","year":"1990","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1039\/D0MO00084A","article-title":"Iron-meditated fungal starvation by lupine rhizosphere-associated and extremotolerant Streptomyces sp. S29 desferrioxamine production","volume":"17","author":"Jarmusch","year":"2021","journal-title":"Mol. Omics"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"455","DOI":"10.3390\/12030455","article-title":"Occurrence, biological activities and synthesis of kaurane diterpenes and their glycosides","volume":"12","author":"Batista","year":"2007","journal-title":"Molecules"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1007\/s12272-018-1078-3","article-title":"Bioactive enmein-type 6,7-seco-ent-kaurane diterpenoids: Natural products, synthetic derivatives and apoptosis related mechanism","volume":"41","author":"Li","year":"2018","journal-title":"Arch. Pharm. Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Becerril, A., \u00c1lvarez, S., Bra\u00f1a, A.F., Rico, S., D\u00edaz, M., Santamar\u00eda, R.I., Salas, J.A., and M\u00e9ndez, C. (2018). Uncovering production of specialized metabolites by Streptomyces argillaceus: Activation of cryptic biosynthesis gene clusters using nutritional and genetic approaches. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0198145"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s10534-014-9739-2","article-title":"Siderophore production by actinobacteria","volume":"27","author":"Wang","year":"2014","journal-title":"Biometals"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Khasheii, B., Mahmoodi, P., and Mohammadzadeh, A. (2021). Siderophores: Importance in bacterial pathogenesis and applications in medicine and industry. Microbiol. Res., 250.","DOI":"10.1016\/j.micres.2021.126790"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Shao, M., Ma, J., Li, Q., and Ju, J. (2019). Identification of the Anti-Infective Aborycin Biosynthetic Gene Cluster from Deep-Sea-Derived Streptomyces sp. SCSIO ZS0098 Enables Production in a Heterologous Host. Mar. Drugs, 17.","DOI":"10.3390\/md17020127"},{"key":"ref_45","unstructured":"(2025, August 30). Available online: https:\/\/www.bioinformatics.babraham.ac.uk\/projects\/trim_galore\/."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1089\/cmb.2013.0084","article-title":"Assembling single-cell genomes and mini-metagenomes from chimeric MDA products","volume":"20","author":"Nurk","year":"2013","journal-title":"J. Comput. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1093\/bioinformatics\/btt086","article-title":"QUAST: Quality assessment tool for genome assemblies","volume":"29","author":"Gurevich","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"W282","DOI":"10.1093\/nar\/gky467","article-title":"The Microbial Genomes Atlas (MiGA) webserver: Taxonomic and gene diversity analysis of Archaea and Bacteria at the whole genome level","volume":"46","author":"Gunturu","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Elmanzalawi, M., Fujisawa, T., Mori, H., Nakamura, Y., and Tanizawa, Y. (2025). DFAST_QC: Quality assessment and taxonomic identification tool for prokaryotic Genomes. BMC Bioinform., 26.","DOI":"10.1186\/s12859-024-06030-y"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Chalita, M., Kim, Y.O., Park, S., Oh, H.-S., Cho, J.H., Moon, J., Baek, N., Moon, C., Lee, K., and Yang, J. (2024). EzBioCloud: A genome-driven database and platform for microbiome identification and discovery. Int. J. Syst. Evol. Microbiol., 74.","DOI":"10.1099\/ijsem.0.006421"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"D801","DOI":"10.1093\/nar\/gkab902","article-title":"TYGS and LPSN: A database tandem for fast and reliable genome-based classification and nomenclature of prokaryotes","volume":"50","author":"Carbasse","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1093\/bioinformatics\/btu153","article-title":"Prokka: Rapid prokaryotic genome annotation","volume":"30","author":"Seemann","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1093\/bib\/bbx146","article-title":"Recent development of antiSMASH and other computational approaches to mine secondary metabolite biosynthetic gene clusters","volume":"20","author":"Blin","year":"2019","journal-title":"Brief Bioinform."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Pluskal, T., Castillo, S., Villar-Briones, A., and Oresic, M. (2010). MZmine 2: Modular Framework for Processing, Visualizing, and Analyzing Mass Spectrometry-Based Molecular Profile Data. BMC Bioinform., 11.","DOI":"10.1186\/1471-2105-11-395"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome. Res."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/23\/10\/404\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T13:11:02Z","timestamp":1760706662000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/23\/10\/404"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,17]]},"references-count":55,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["md23100404"],"URL":"https:\/\/doi.org\/10.3390\/md23100404","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,17]]}}}