{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:07:00Z","timestamp":1790809620553,"version":"4.1.0"},"reference-count":17,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T00:00:00Z","timestamp":1705363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Marie Curie International Incoming Fellowship Grant","award":["274110"],"award-info":[{"award-number":["274110"]}]},{"name":"Marie Curie International Incoming Fellowship Grant","award":["311848"],"award-info":[{"award-number":["311848"]}]},{"name":"Marie Curie International Incoming Fellowship Grant","award":["ACH7\u2014BDTP18"],"award-info":[{"award-number":["ACH7\u2014BDTP18"]}]},{"name":"Marie Curie International Incoming Fellowship Grant","award":["GA2016_005OS"],"award-info":[{"award-number":["GA2016_005OS"]}]},{"name":"Marie Curie International Incoming Fellowship Grant","award":["EP\/T020237\/1"],"award-info":[{"award-number":["EP\/T020237\/1"]}]},{"name":"European Commission","award":["274110"],"award-info":[{"award-number":["274110"]}]},{"name":"European Commission","award":["311848"],"award-info":[{"award-number":["311848"]}]},{"name":"European Commission","award":["ACH7\u2014BDTP18"],"award-info":[{"award-number":["ACH7\u2014BDTP18"]}]},{"name":"European Commission","award":["GA2016_005OS"],"award-info":[{"award-number":["GA2016_005OS"]}]},{"name":"European Commission","award":["EP\/T020237\/1"],"award-info":[{"award-number":["EP\/T020237\/1"]}]},{"name":"EastBio","award":["274110"],"award-info":[{"award-number":["274110"]}]},{"name":"EastBio","award":["311848"],"award-info":[{"award-number":["311848"]}]},{"name":"EastBio","award":["ACH7\u2014BDTP18"],"award-info":[{"award-number":["ACH7\u2014BDTP18"]}]},{"name":"EastBio","award":["GA2016_005OS"],"award-info":[{"award-number":["GA2016_005OS"]}]},{"name":"EastBio","award":["EP\/T020237\/1"],"award-info":[{"award-number":["EP\/T020237\/1"]}]},{"name":"British Society for Antimicrobial Chemotherapy","award":["274110"],"award-info":[{"award-number":["274110"]}]},{"name":"British Society for Antimicrobial Chemotherapy","award":["311848"],"award-info":[{"award-number":["311848"]}]},{"name":"British Society for Antimicrobial Chemotherapy","award":["ACH7\u2014BDTP18"],"award-info":[{"award-number":["ACH7\u2014BDTP18"]}]},{"name":"British Society for Antimicrobial Chemotherapy","award":["GA2016_005OS"],"award-info":[{"award-number":["GA2016_005OS"]}]},{"name":"British Society for Antimicrobial Chemotherapy","award":["EP\/T020237\/1"],"award-info":[{"award-number":["EP\/T020237\/1"]}]},{"name":"Equitable access to Quality Antibiotic Therapies in Africa","award":["274110"],"award-info":[{"award-number":["274110"]}]},{"name":"Equitable access to Quality Antibiotic Therapies in Africa","award":["311848"],"award-info":[{"award-number":["311848"]}]},{"name":"Equitable access to Quality Antibiotic Therapies in Africa","award":["ACH7\u2014BDTP18"],"award-info":[{"award-number":["ACH7\u2014BDTP18"]}]},{"name":"Equitable access to Quality Antibiotic Therapies in Africa","award":["GA2016_005OS"],"award-info":[{"award-number":["GA2016_005OS"]}]},{"name":"Equitable access to Quality Antibiotic Therapies in Africa","award":["EP\/T020237\/1"],"award-info":[{"award-number":["EP\/T020237\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>With the rise in antimicrobial resistance, there is an urgent need for new classes of antibiotic with which to treat infectious disease. Marinomycin, a polyene antibiotic from a marine microbe, has been shown capable of killing methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF), as well as having promising activity against melanoma. An attractive solution to the photoprotection of this antibiotic has been demonstrated. Here, we report the identification and analysis of the marinomycin biosynthetic gene cluster (BGC), and the biosynthetic assembly of the macrolide. The marinomycin BGC presents a challenge in heterologous expression due to its large size and high GC content, rendering the cluster prone to rearrangement. We demonstrate the transformation of Streptomyces lividans using a construct containing the cluster, and the heterologous expression of the encoded biosynthetic machinery and production of marinomycin B.<\/jats:p>","DOI":"10.3390\/biom14010117","type":"journal-article","created":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T08:12:37Z","timestamp":1705392757000},"page":"117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Identification and Heterologous Expression of the Biosynthetic Gene Cluster Encoding the Antibiotic and Anticancer Agent Marinomycin"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8343-2524","authenticated-orcid":false,"given":"Emily","family":"Abraham","sequence":"first","affiliation":[{"name":"Department of Chemistry & BSRC, University of St. Andrews, St. Andrews KY16 9ST, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah A.","family":"Lawther","sequence":"additional","affiliation":[{"name":"Department of Chemistry & BSRC, University of St. Andrews, St. Andrews KY16 9ST, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunpeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry & BSRC, University of St. Andrews, St. Andrews KY16 9ST, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph S.","family":"Zarins-Tutt","sequence":"additional","affiliation":[{"name":"Department of Chemistry & BSRC, University of St. Andrews, St. Andrews KY16 9ST, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerry Sann","family":"Rivera","sequence":"additional","affiliation":[{"name":"Intact Genomics, St. Louis, MO 63132, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengcang","family":"Wu","sequence":"additional","affiliation":[{"name":"Intact Genomics, St. Louis, MO 63132, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3643-5578","authenticated-orcid":false,"given":"Jack A.","family":"Connolly","sequence":"additional","affiliation":[{"name":"Department of Chemistry & BSRC, University of St. Andrews, St. Andrews KY16 9ST, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon","family":"Florence","sequence":"additional","affiliation":[{"name":"Department of Chemistry & BSRC, University of St. Andrews, St. Andrews KY16 9ST, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8210-306X","authenticated-orcid":false,"given":"Matthias","family":"Agbo","sequence":"additional","affiliation":[{"name":"Department of Chemistry & BSRC, University of St. Andrews, St. Andrews KY16 9ST, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Chemistry & BSRC, University of St. Andrews, St. Andrews KY16 9ST, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca J. M.","family":"Goss","sequence":"additional","affiliation":[{"name":"Department of Chemistry & BSRC, University of St. Andrews, St. Andrews KY16 9ST, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,16]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2024, January 12). Removing Obstacles to Healthy Development: Report on Infectious Diseases. Available online: https:\/\/apps.who.int\/iris\/handle\/10665\/65847."},{"key":"ref_2","unstructured":"Roxby, P. (BBC, 2021). Hidden pandemic of antibiotic-resistant infections, health officials warn, BBC."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/s41429-020-0291-8","article-title":"Antibiotics in the clinical pipeline in October 2019","volume":"73","author":"Butler","year":"2020","journal-title":"J. Antibiot."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.2174\/0929867043365044","article-title":"Polyene macrolide antibiotic biosynthesis","volume":"11","author":"Aparicio","year":"2004","journal-title":"Curr. Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s00253-002-1183-5","article-title":"Polyene antibiotic biosynthesis gene clusters","volume":"61","author":"Aparicio","year":"2002","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1021\/ja0558948","article-title":"Marinomycins A-D, antitumor-antibiotics of a new structure class from a marine actinomycete of the recently discovered genus \u201cMarinispora\u201d","volume":"128","author":"Kwon","year":"2006","journal-title":"Am. Chem. Soc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1039\/b304027e","article-title":"Photochemical reactivity of polyenes: From dienes to rhodopsin, from microseconds to femtoseconds","volume":"2","author":"Liu","year":"2003","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7549","DOI":"10.1039\/C9SC01375J","article-title":"A natural solution to photoprotection and isolation of the potent polyene antibiotic, marinomycin A","volume":"10","author":"Bailey","year":"2019","journal-title":"Chem. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5607","DOI":"10.1128\/jb.170.12.5607-5612.1988","article-title":"Characterization of a unique methyl-specific restriction system in Streptomyces avermitilis","volume":"170","author":"MacNeil","year":"1988","journal-title":"J. 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Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1038\/s41467-017-01344-3","article-title":"Diversity oriented biosynthesis via accelerated evolution of modular gene clusters","volume":"8","author":"Wlodek","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/73810","article-title":"Artificial chromosomes for antibiotic-producing actinomycetes","volume":"18","author":"Sosio","year":"2000","journal-title":"Nat. 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