{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:00:00Z","timestamp":1772118000263,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"am","delay-in-days":365,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech &amp; Bioengineering"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Microbial\u2010derived natural products remain a major source of structurally diverse bioactive compounds and chemical scaffolds that have the potential as new therapeutics to target drug\u2010resistant pathogens and cancers. In particular, genome mining has revealed the vast number of cryptic or low\u2010yield biosynthetic gene clusters in the genus\n                    <jats:italic>Streptomyces<\/jats:italic>\n                    . However, low natural product yields\u2014improvements to which have been hindered by the lack of high throughput methods\u2014have slowed the discovery and development of many potential therapeutics. Here, we describe our efforts to improve yields of landomycins\u2014angucycline family polyketides under investigation as cancer therapeutics\u2014by a genetically modified\n                    <jats:italic>Streptomyces cyanogenus<\/jats:italic>\n                    136. After simplifying the extraction process from\n                    <jats:italic>S. cyanogenus<\/jats:italic>\n                    cultures, we identified a wavelength at which the major landomycin products are absorbed in culture extracts, which we used to systematically explore culture medium compositions to improve total landomycin titers. Through correlational analysis, we simplified the culture optimization process by identifying an alternative wavelength at which culture supernatants absorb yet is representative of total landomycin titers. Using the subsequently improved sample throughput, we explored landomycin production during the culturing process to further increase landomycin yield and reduce culture time. Testing the antimicrobial activity of the isolated landomycins, we report broad inhibition of Gram\u2010positive bacteria, inhibition of fungi by landomycinone, and broad landomycin resistance by Gram\u2010negative bacteria that is likely mediated by the exclusion of landomycins by the bacterial membrane. Finally, the anticancer activity of the isolated landomycins against A549 lung carcinoma cells agrees with previous reports on other cell lines that glycan chain length correlates with activity. Given the prevalence of natural products produced by\n                    <jats:italic>Streptomyces<\/jats:italic>\n                    , as well as the light\u2010absorbing moieties common to bioactive natural products and their metabolic precursors, our method is relevant to improving the yields of other natural products of interest.\n                  <\/jats:p>","DOI":"10.1002\/bit.28725","type":"journal-article","created":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T07:45:06Z","timestamp":1714463106000},"page":"2648-2661","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rapid spectrophotometric detection for optimized production of landomycins and characterization of their therapeutic potential"],"prefix":"10.1002","volume":"121","author":[{"given":"Todd C.","family":"Chappell","sequence":"first","affiliation":[{"name":"Department of Chemical &amp; Biological Engineering Tufts University Medford Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen G.","family":"Maiello","sequence":"additional","affiliation":[{"name":"Department of Chemistry Tufts University Medford Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allison J.","family":"Tierney","sequence":"additional","affiliation":[{"name":"Department of Chemistry Tufts University Medford Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Yanagi","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; Biological Engineering Tufts University Medford Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica A.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; Biological Engineering Tufts University Medford Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyongbum","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; Biological Engineering Tufts University Medford Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles R.","family":"Mace","sequence":"additional","affiliation":[{"name":"Department of Chemistry Tufts University Medford Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clay S.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Department of Chemistry Tufts University Medford Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7737-1385","authenticated-orcid":false,"given":"Nikhil U.","family":"Nair","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; Biological Engineering Tufts University Medford Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-58904-9"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/2071391a0"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo1018377"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/msystems.00489-21"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(99)00261-9"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202114850"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1103921108"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.201500297"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja973348b"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4510"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.43.492"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13205-021-02834-4"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1039\/C1NP00068C"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2007.08.026"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1RA01088C"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201812222"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2020.06.024"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.15407\/ubj87.05.072"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804348105"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2020.08.006"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.200400316"},{"key":"e_1_2_9_23_1","first-page":"31","article-title":"[The sensitivity to landomycins A and E of streptomycetes, producers of polyketide antibiotics]","volume":"60","author":"Matseliukh B. 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