{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T03:49:18Z","timestamp":1781322558761,"version":"3.54.1"},"reference-count":41,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32060021"],"award-info":[{"award-number":["32060021"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004479","name":"Natural Science Foundation of Jiangxi Province","doi-asserted-by":"crossref","award":["20242BAB25337"],"award-info":[{"award-number":["20242BAB25337"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004479","name":"Natural Science Foundation of Jiangxi Province","doi-asserted-by":"crossref","award":["20232BAB206148"],"award-info":[{"award-number":["20232BAB206148"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>The endophytic Streptomyces sp. PRh3 (PRh3), isolated from Dongxiang wild rice (DXWR), exhibited impaired biosynthetic capacity in the laboratory. To address this defect, rifampicin-based ribosome engineering was first applied to PRh3 to generate PRh3-r55, which acquired a characteristic H473Y rifampicin-resistant mutation in rpoB to activate the production of two \u03b2-carboline alkaloids JBIR-133 and JBIR-134. Then the biosynthetic gene cluster (BGC) ksl was introduced into PRh3-r55 for heterologous expression, generating PRh3-r55K. This combined approach achieved a synergistic effect, enabling the strain to produce not only the expected JBIR-133, JBIR-134, and kitasetaline, but also a novel sulfur-containing molecule, novkitasetaline. Structural elucidation identified novkitasetaline as a unique tryptamine-substituted kitasetaline derivative at the C-3 position of its pyridine ring. Notably, this structural modification conferred significant antimalarial activity to novkitasetaline, rendering it active against drug-sensitive Plasmodium falciparum 3D7 (IC50 = 32.65 \u00b1 2.93 \u03bcM) and three other drug-resistant P. falciparum strains: K13C580Y, Dd2, and HB3 (IC50 = 45.98 \u00b1 4.17~59.67 \u00b1 3.15 \u03bcM), primarily by disrupting late-stage parasite development. These efforts not only identified a promising antimalarial lead compound but also demonstrated that combining ribosome engineering with heterologous expression is an effective strategy for discovering bioactive natural products from Streptomyces.<\/jats:p>","DOI":"10.3390\/microorganisms13122871","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T09:15:21Z","timestamp":1766049321000},"page":"2871","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mining of Novkitasetaline, a New Sulfur-Containing Antimalarial \u03b2-Carboline Alkaloid, from Streptomyces sp. PRh3 by Functional Ribosome Engineering Directed Heterologous Expression"],"prefix":"10.3390","volume":"13","author":[{"given":"Xingyu","family":"Chen","sequence":"first","affiliation":[{"name":"Key Laboratory of Biodiversity Conservation and Bioresource Utilization of Jiangxi Province, College of Life Sciences, Jiangxi Normal University, Nanchang 330022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"He","sequence":"additional","affiliation":[{"name":"National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi 214064, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmin","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biodiversity Conservation and Bioresource Utilization of Jiangxi Province, College of Life Sciences, Jiangxi Normal University, Nanchang 330022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangping","family":"Feng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biodiversity Conservation and Bioresource Utilization of Jiangxi Province, College of Life Sciences, Jiangxi Normal University, Nanchang 330022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihan","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biodiversity Conservation and Bioresource Utilization of Jiangxi Province, College of Life Sciences, Jiangxi Normal University, Nanchang 330022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhui","family":"Song","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biodiversity Conservation and Bioresource Utilization of Jiangxi Province, College of Life Sciences, Jiangxi Normal University, Nanchang 330022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1339-3558","authenticated-orcid":false,"given":"Xinyu","family":"Yu","sequence":"additional","affiliation":[{"name":"National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi 214064, China"},{"name":"Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4042-9405","authenticated-orcid":false,"given":"Yunchang","family":"Xie","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biodiversity Conservation and Bioresource Utilization of Jiangxi Province, College of Life Sciences, Jiangxi Normal University, Nanchang 330022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1039\/C7NP00026J","article-title":"Actinomycetes: Still a source of novel antibiotics","volume":"34","author":"Genilloud","year":"2017","journal-title":"Nat. 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