{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T12:05:45Z","timestamp":1776427545300,"version":"3.51.2"},"reference-count":82,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2022YFC2105303"],"award-info":[{"award-number":["2022YFC2105303"]}]},{"name":"National Key Research and Development Program of China","award":["2018YFC1800400"],"award-info":[{"award-number":["2018YFC1800400"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["51909282"],"award-info":[{"award-number":["51909282"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004761","name":"Natural Science Foundation of Hunan Province of China","doi-asserted-by":"crossref","award":["2022JJ40583"],"award-info":[{"award-number":["2022JJ40583"]}],"id":[{"id":"10.13039\/501100004761","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Hunan Provincial Key Research and Development Plan","award":["2022WK2017"],"award-info":[{"award-number":["2022WK2017"]}]},{"name":"Hunan Provincial Key Research and Development Plan","award":["2023NK2030"],"award-info":[{"award-number":["2023NK2030"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Acid mine drainage (AMD) environments feature extreme acidity (pH \u2264 2) and high heavy metal concentrations. Acidophiles survive these conditions through unique genetic adaptations and secondary metabolite (SM) pathways. Leptospirillum ferriphilum, known for its acid and heavy metal resistance, serves as a model for AMD bioremediation, though systematic multi-omics studies on its key SMs and biosynthesis pathways remain underexplored. In this study, L. ferriphilum YR01 was isolated and identified from the AMD of the Zijinshan copper mine, China. Pangenomic analysis revealed that YR01 possesses the largest number of genes (2623) among the eight sequenced L. ferriphilum strains. Comparative genomics, antiSMASH, BiG-SCAPE, and metabolomic analyses (LC-MS and HPLC-MS) were integrated to comprehensively explore its biosynthetic capacity. A total of 39 biosynthetic gene clusters (BGCs) were identified, of which 60% shared &lt;50% similarity with known clusters, indicating substantial novel biosynthetic potential. The sequence alignment of SM biosynthetic gene clusters (BGCs) demonstrated the potential of L. ferriphilum to synthesize conserved clusters for ectoine, choline, carotenoids, terpenoids, and terpene precursors. YR01 harbors complete BGCs for all five SM types. Notably, key nonribosomal peptide synthetase (NRPS) modules implicated in N-acyl homoserine lactone (AHL) synthesis were identified. Untargeted metabolomics (LC-MS) revealed the production of diverse SMs (18 types) putatively involved in environmental adaptation, including phosphocholine, carotenoids (e.g., anteraxanthin), cholera autoinducer-1 (CAI-1), and multiple AHLs. Targeted detection (HPLC-MS) further confirmed that YR01 could produce ectoine (0.10 ng\/mL) and specific AHLs (C14-HSL, C12-HSL, C12-OH-HSL), which were beneficial for the survival of the strain in extremely acidic environments and interspecies communication through SMs. This study represents the first comprehensive multi-omics characterization of BGCs in L. ferriphilum and experimentally validates the production of key SMs. Collectively, this study provides a comprehensive elucidation of the SM biosynthetic repertoire and environmental adaptation strategies in L. ferriphilum, advancing our understanding of microbial adaptation and interspecies communication in AMD systems, and offering potential implications for biomining applications.<\/jats:p>","DOI":"10.3390\/microorganisms13112493","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T02:48:28Z","timestamp":1761878908000},"page":"2493","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Integrative Multi-Omics Identify Key Secondary Metabolites Linked to Acid Tolerance in Leptospirillum ferriphilum"],"prefix":"10.3390","volume":"13","author":[{"given":"Yiran","family":"Li","sequence":"first","affiliation":[{"name":"School of Minerals Processing and Bioengineering, Central South University, Changsha 410083, China"},{"name":"Key Laboratory of Biohydrometallurgy, Ministry of Education, Changsha 410083, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiejie","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Minerals Processing and Bioengineering, Central South University, Changsha 410083, China"},{"name":"Key Laboratory of Biohydrometallurgy, Ministry of Education, Changsha 410083, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha 410031, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luhua","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Minerals Processing and Bioengineering, Central South University, Changsha 410083, China"},{"name":"Key Laboratory of Biohydrometallurgy, Ministry of Education, Changsha 410083, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiqi","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Minerals Processing and Bioengineering, Central South University, Changsha 410083, China"},{"name":"Key Laboratory of Biohydrometallurgy, Ministry of Education, Changsha 410083, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manjun","family":"Miao","sequence":"additional","affiliation":[{"name":"School of Minerals Processing and Bioengineering, Central South University, Changsha 410083, China"},{"name":"Key Laboratory of Biohydrometallurgy, Ministry of Education, Changsha 410083, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yili","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Minerals Processing and Bioengineering, Central South University, Changsha 410083, China"},{"name":"Key Laboratory of Biohydrometallurgy, Ministry of Education, Changsha 410083, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueduan","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Minerals Processing and Bioengineering, Central South University, Changsha 410083, China"},{"name":"Key Laboratory of Biohydrometallurgy, Ministry of Education, Changsha 410083, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1016\/S1003-6326(09)60008-X","article-title":"Microbial aspects of acid mine drainage and its bioremediation","volume":"18","author":"Natarajan","year":"2008","journal-title":"Trans Nonferrous Met. 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