{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:49:57Z","timestamp":1792784997763,"version":"4.5.0"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T00:00:00Z","timestamp":1710979200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T00:00:00Z","timestamp":1710979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Centre of Excellence for Biomedical Tuberculosis Research"},{"name":"South African Medical Research Association Council"},{"DOI":"10.13039\/501100001866","name":"National Research Fund","doi-asserted-by":"crossref","award":["NRF GRANT UID129364"],"award-info":[{"award-number":["NRF GRANT UID129364"]}],"id":[{"id":"10.13039\/501100001866","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Mycobacterial pathogens present a significant challenge to disease control efforts globally due to their inherent resistance to multiple antibiotics. The rise of drug-resistant strains of\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    has prompted an urgent need for innovative therapeutic solutions. One promising way to discover new tuberculosis drugs is by utilizing natural products from the vast biochemical space. Multidisciplinary methods can used to harness the bioactivity of these natural products. This study aimed to evaluate the antimycobacterial efficacy of functional crude extracts from bacteria isolated from gold mine tailings in South Africa. Bacterial strains were identified using 16S rRNA sequencing. The crude extracts obtained from the bacteria were tested against\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    H37Rv,\n                    <jats:italic>Mycobacterium smegmatis<\/jats:italic>\n                    mc\n                    <jats:sup>2<\/jats:sup>\n                    155, and\n                    <jats:italic>Mycobacterium aurum<\/jats:italic>\n                    A+. Untargeted HPLC-qTOF and molecular networking were used to identify the functional constituents present in extracts that exhibited inhibitory activity. A virtual screening workflow (VSW) was used to filter compounds that were strong binders to\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    Pks13 and PknG. The ligands returned from the VSW were subjected to optimization using density functional theory (DFT) at M06-2X\/6-311++ (\n                    <jats:italic>d,p<\/jats:italic>\n                    ) level of theory and basis set implemented in Gaussian16 Rev.C01. The optimized ligands were re-docked against\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    Pks13 and PknG. Molecular dynamics simulation and molecular mechanics generalized born surface area were used to evaluate the stability of the protein\u2013ligand complexes formed by the identified hits. The hit that showed promising binding characteristics was virtually modified through multiple synthetic routes using reaction-driven enumeration. Three bacterial isolates showed significant activity against the two strains of\n                    <jats:italic>Mycobacterium<\/jats:italic>\n                    , while only two,\n                    <jats:italic>Bacillus subtilis<\/jats:italic>\n                    and\n                    <jats:italic>Bacillus licheniformis<\/jats:italic>\n                    , exhibited activity against both\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    H37Rv,\n                    <jats:italic>Mycobacterium smegmatis<\/jats:italic>\n                    mc\n                    <jats:sup>2<\/jats:sup>\n                    155, and\n                    <jats:italic>Mycobacterium aurum<\/jats:italic>\n                    A+. The tentatively identified compounds from the bacterial crude extracts belonged to various classes of natural compounds associated with antimicrobial activity. Two compounds, cyclo-(L-Pro-4-OH-L-Leu) and vazabitide A, showed strong binding against PknG and Pks13, with pre-MD MM-GBSA values of \u2212\u00a042.8\u00a0kcal\/mol and \u2212\u00a047.6\u00a0kcal\/mol, respectively. The DFT-optimized compounds exhibited the same docking scores as the ligands optimized using the OPSL-4 force field. After modifying vazabitide A, its affinity to the Pks13 binding site increased to \u2212\u00a085.8\u00a0kcal\/mol, as revealed by the post-MD MM-GBSA analysis. This study highlights the potential of bacteria isolates from gold mine tailings as a source of new scaffolds for designing and optimizing anti-\n                    <jats:italic>Mycobacterium<\/jats:italic>\n                    agents. These agents synthesized in-silico can be further tested in-vitro to evaluate their efficacy.\n                  <\/jats:p>","DOI":"10.1038\/s41598-024-57124-9","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T07:01:57Z","timestamp":1711004517000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Molecular docking, molecular dynamics simulations and binding free energy studies of interactions between Mycobacterium tuberculosis Pks13, PknG and bioactive constituents of extremophilic bacteria"],"prefix":"10.1038","volume":"14","author":[{"given":"Kudakwashe","family":"Nyambo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kudzanai Ian","family":"Tapfuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Adu-Amankwaah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Julius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucinda","family":"Baatjies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Idah Sithole","family":"Niang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liezel","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna Kuben","family":"Govender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mkhuseli","family":"Ngxande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Watson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubbe","family":"Wiesner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vuyo","family":"Mavumengwana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,21]]},"reference":[{"key":"57124_CR1","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.3389\/fmicb.2018.01517","volume":"9","author":"Y Kanehiro","year":"2018","unstructured":"Kanehiro, Y. et al. Identification of novel mycobacterial inhibitors against mycobacterial protein kinase G. Front. Microbiol. 9, 1517 (2018).","journal-title":"Front. Microbiol."},{"key":"57124_CR2","unstructured":"World TB Day 2023. https:\/\/www.who.int\/campaigns\/world-tb-day\/2023"},{"key":"57124_CR3","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1039\/C3MD00251A","volume":"5","author":"JD Guzman","year":"2013","unstructured":"Guzman, J. D. et al. 2-Hydroxy-substituted cinnamic acids and acetanilides are selective growth inhibitors of Mycobacterium tuberculosis. Medchemcomm 5, 47\u201350 (2013).","journal-title":"Medchemcomm"},{"key":"57124_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13568-022-01348-3","volume":"12","author":"SS Barale","year":"2022","unstructured":"Barale, S. S., Ghane, S. G. & Sonawane, K. D. Purification and characterization of antibacterial surfactin isoforms produced by Bacillus velezensis SK. AMB Express 12, 1\u201320 (2022).","journal-title":"AMB Express"},{"key":"57124_CR5","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1021\/np100853e","volume":"74","author":"A Hamdache","year":"2011","unstructured":"Hamdache, A., Lamarti, A., Aleu, J. & Collado, I. G. Non-peptide metabolites from the genus Bacillus. J. Nat. Prod 74, 893\u2013899 (2011).","journal-title":"J. Nat. Prod"},{"key":"57124_CR6","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.01490","author":"L Morelli","year":"2017","unstructured":"Morelli, L. et al. Bacillus as potential probiotics: Status, concerns, and future perspectives. Front. Microbiol. https:\/\/doi.org\/10.3389\/fmicb.2017.01490 (2017).","journal-title":"Front. Microbiol."},{"key":"57124_CR7","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1007\/s00203-008-0409-z","volume":"190","author":"A Etchegaray","year":"2008","unstructured":"Etchegaray, A. et al. Effect of a highly concentrated lipopeptide extract of Bacillus subtilis on fungal and bacterial cells. Arch. Microbiol. 190, 611\u2013622 (2008).","journal-title":"Arch. Microbiol."},{"key":"57124_CR8","doi-asserted-by":"publisher","first-page":"3107","DOI":"10.3389\/fmicb.2019.03107","volume":"10","author":"DB Medeot","year":"2020","unstructured":"Medeot, D. B., Fernandez, M., Morales, G. M. & Jofr\u00e9, E. Fengycins from Bacillus amyloliquefaciens MEP218 exhibit antibacterial activity by producing alterations on the cell surface of the pathogens Xanthomonas axonopodis pv. vesicatoria and Pseudomonas aeruginosa PA01. Front. Microbiol. 10, 3107 (2020).","journal-title":"Front. Microbiol."},{"key":"57124_CR9","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1016\/j.tim.2017.02.001","volume":"25","author":"SE Jones","year":"2017","unstructured":"Jones, S. E. & Elliot, M. A. Streptomyces exploration: Competition, volatile communication and new bacterial behaviours. Trends Microbiol. 25, 522\u2013531 (2017).","journal-title":"Trends Microbiol."},{"key":"57124_CR10","doi-asserted-by":"publisher","first-page":"460","DOI":"10.3390\/molecules25030460","volume":"25","author":"Q Fang","year":"2020","unstructured":"Fang, Q. et al. Signalling and bioactive metabolites from Streptomyces sp. RK44. Molecules 25, 460 (2020).","journal-title":"Molecules"},{"key":"57124_CR11","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1128\/AAC.00558-10","volume":"55","author":"JB Bruning","year":"2011","unstructured":"Bruning, J. B., Murillo, A. C., Chacon, O., Barletta, R. G. & Sacchettini, J. C. Structure of the Mycobacterium tuberculosis D-alanine: D-alanine ligase, a target of the antituberculosis drug D-cycloserine. Antimicrob. Agents Chemother. 55, 291\u2013301 (2011).","journal-title":"Antimicrob. Agents Chemother."},{"key":"57124_CR12","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1002\/emmm.201201689","volume":"4","author":"RC Hartkoorn","year":"2012","unstructured":"Hartkoorn, R. C. et al. Towards a new tuberculosis drug: Pyridomycin\u2014Nature\u2019s isoniazid. EMBO Mol. Med. 4, 1032\u20131042 (2012).","journal-title":"EMBO Mol. Med."},{"key":"57124_CR13","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph13111047","author":"MO Fashola","year":"2016","unstructured":"Fashola, M. O., Ngole-Jeme, V. M. & Babalola, O. O. Heavy metal pollution from gold mines: Environmental effects and bacterial strategies for resistance. Int. J. Environ. Res. Public Health https:\/\/doi.org\/10.3390\/ijerph13111047 (2016).","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"57124_CR14","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1128\/JB.06359-11","volume":"194","author":"Y Lin","year":"2012","unstructured":"Lin, Y. et al. Draft genome sequence of Halomonas sp. strain HAL1, a moderately halophilic arsenite-oxidizing bacterium isolated from gold-mine soil. J. Bacteriol. 194, 199\u2013200. https:\/\/doi.org\/10.1128\/JB.06359-11 (2012).","journal-title":"J. Bacteriol."},{"key":"57124_CR15","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1093\/femsec\/fiaa111","volume":"96","author":"SK Sanyal","year":"2020","unstructured":"Sanyal, S. K., Reith, F. & Shuster, J. A genomic perspective of metal-resistant bacteria from gold particles: Possible survival mechanisms during gold biogeochemical cycling. FEMS Microbiol. Ecol. 96, 111 (2020).","journal-title":"FEMS Microbiol. Ecol."},{"key":"57124_CR16","doi-asserted-by":"publisher","first-page":"320","DOI":"10.3390\/metabo12040320","volume":"12","author":"YY Chen","year":"2022","unstructured":"Chen, Y. Y. et al. Probing anti-leukemic metabolites from marine-derived Streptomyces sp. LY1209. Metabolites 12, 320 (2022).","journal-title":"Metabolites"},{"key":"57124_CR17","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1038\/s43247-021-00105-x","volume":"2","author":"T Milojevic","year":"2021","unstructured":"Milojevic, T. et al. Chemolithotrophy on the Noachian Martian breccia NWA 7034 via experimental microbial biotransformation. Commun. Earth Environ. 2, 39 (2021).","journal-title":"Commun. Earth Environ."},{"key":"57124_CR18","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1093\/oxfordjournals.molbev.a026203","volume":"16","author":"S Garcia-Vallve","year":"1999","unstructured":"Garcia-Vallve, S., Palan, J. & Romeu, A. Horizontal gene transfer in glycosyl hydrolases inferred from codon usage in Escherichia coli and Bacillus subtilis. Mol. Biol. Evol. 16, 1125\u20131134 (1999).","journal-title":"Mol. Biol. Evol."},{"key":"57124_CR19","doi-asserted-by":"publisher","first-page":"1995","DOI":"10.1007\/s00203-020-02173-7","volume":"203","author":"S Santhi Sudha","year":"2021","unstructured":"Santhi Sudha, S. & Aranganathan, V. Experimental elucidation of an antimycobacterial bacteriocin produced by ethnomedicinal plant-derived Bacillus subtilis (MK733983). Arch. Microbiol. 203, 1995\u20132006 (2021).","journal-title":"Arch. Microbiol."},{"key":"57124_CR20","doi-asserted-by":"publisher","first-page":"2361","DOI":"10.1021\/acs.accounts.0c00878","volume":"54","author":"V Singh","year":"2021","unstructured":"Singh, V. & Chibale, K. Strategies to combat multi-drug resistance in tuberculosis. Acc. Chem. Res. 54, 2361\u20132376 (2021).","journal-title":"Acc. Chem. Res."},{"key":"57124_CR21","doi-asserted-by":"publisher","first-page":"e02192-91","DOI":"10.1128\/aac.02192-21","volume":"66","author":"GS Basarab","year":"2022","unstructured":"Basarab, G. S. et al. Spiropyrimidinetriones: A class of DNA gyrase inhibitors with activity against mycobacterium tuberculosis and without cross-resistance to fluoroquinolones. Antimicrob. Agents Chemother. 66, e02192-91 (2022).","journal-title":"Antimicrob. Agents Chemother."},{"key":"57124_CR22","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.cmi.2016.10.022","volume":"23","author":"T Sch\u00f6n","year":"2017","unstructured":"Sch\u00f6n, T. et al. Mycobacterium tuberculosis drug-resistance testing: Challenges, recent developments and perspectives. Clin. Microbiol. Infect. 23, 154\u2013160. https:\/\/doi.org\/10.1016\/j.cmi.2016.10.022 (2017).","journal-title":"Clin. Microbiol. Infect."},{"key":"57124_CR23","doi-asserted-by":"publisher","first-page":"e165","DOI":"10.1016\/S2666-5247(20)30031-8","volume":"1","author":"C Nimmo","year":"2020","unstructured":"Nimmo, C. et al. Population-level emergence of bedaquiline and clofazimine resistance-associated variants among patients with drug-resistant tuberculosis in southern Africa: A phenotypic and phylogenetic analysis. Lancet Microbe 1, e165\u2013e174 (2020).","journal-title":"Lancet Microbe"},{"key":"57124_CR24","doi-asserted-by":"crossref","unstructured":"Kidwai, S. et al. NU-6027 Inhibits growth of Mycobacterium tuberculosis by targeting protein kinase D and protein kinase G (2019). http:\/\/aac.asm.org\/","DOI":"10.1128\/AAC.00996-19"},{"key":"57124_CR25","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.tim.2021.11.005","volume":"30","author":"SN Nagarajan","year":"2022","unstructured":"Nagarajan, S. N., Lenoir, C. & Grangeasse, C. Recent advances in bacterial signaling by serine\/threonine protein kinases. Trends Microbiol. 30, 553\u2013566 (2022).","journal-title":"Trends Microbiol."},{"key":"57124_CR26","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1039\/D0NJ03828H","volume":"45","author":"G Zhao","year":"2021","unstructured":"Zhao, G. et al. The structure-based virtual screening of non-benzofuran inhibitors against: M. tuberculosis Pks13-TE for anti-tuberculosis phenotypic discovery. New J. Chem 45, 1286\u20131300 (2021).","journal-title":"New J. Chem"},{"key":"57124_CR27","doi-asserted-by":"publisher","first-page":"2","DOI":"10.3390\/metabo6010002","volume":"6","author":"K Purves","year":"2016","unstructured":"Purves, K. et al. Using molecular networking for microbial secondary metabolite bioprospecting. Metabolites 6, 2 (2016).","journal-title":"Metabolites"},{"key":"57124_CR28","doi-asserted-by":"publisher","first-page":"498","DOI":"10.3390\/md17090498","volume":"17","author":"L Xu","year":"2019","unstructured":"Xu, L. et al. Comparative genomic insights into secondary metabolism biosynthetic gene cluster distributions of marine streptomyces. Mar. Drugs 17, 498 (2019).","journal-title":"Mar. Drugs"},{"key":"57124_CR29","doi-asserted-by":"publisher","first-page":"8466","DOI":"10.1038\/s41598-017-08445-5","volume":"7","author":"D Lecina","year":"2017","unstructured":"Lecina, D., Gilabert, J. F. & Guallar, V. Adaptive simulations, towards interactive protein-ligand modeling. Sci. Rep. 7, 8466 (2017).","journal-title":"Sci. Rep."},{"key":"57124_CR30","doi-asserted-by":"publisher","first-page":"2827","DOI":"10.1021\/acs.jmedchem.1c00320","volume":"65","author":"Q Wang","year":"2022","unstructured":"Wang, Q. et al. Probing the allosteric inhibition mechanism of a spike protein using molecular dynamics simulations and active compound identifications. J. Med. Chem. 65, 2827\u20132835 (2022).","journal-title":"J. Med. Chem."},{"key":"57124_CR31","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1094\/PBIOMES-09-21-0054-A","volume":"6","author":"P Yang","year":"2022","unstructured":"Yang, P., Bokros, N., Debolt, S., Zhao, Z. & Xia, Y. Genome sequence source of Bacillus amyloliquefaciens strain GD4a, a bacterial endophyte associated with switchgrass plants. Phytobiomes J. 6, 354\u2013357 (2022).","journal-title":"Phytobiomes J."},{"key":"57124_CR32","first-page":"1","volume":"9","author":"K Nyambo","year":"2020","unstructured":"Nyambo, K. & Sithole Niang, I. Bioprospecting of endophytes isolated from selected Zimbabwean medicinal plants. WJEB 9, 1\u201312 (2020).","journal-title":"WJEB"},{"key":"57124_CR33","doi-asserted-by":"publisher","first-page":"1870","DOI":"10.1093\/molbev\/msw054","volume":"33","author":"S Kumar","year":"2016","unstructured":"Kumar, S., Stecher, G. & Tamura, K. MEGA7: Molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol. Biol. Evol. 33, 1870\u20131874 (2016).","journal-title":"Mol. Biol. Evol."},{"key":"57124_CR34","doi-asserted-by":"publisher","first-page":"602","DOI":"10.3390\/ijerph16040602","volume":"16","author":"N Uche-Okereafor","year":"2019","unstructured":"Uche-Okereafor, N. et al. Antibacterial activities of crude secondary metabolite extracts from pantoea species obtained from the stem of solanum mauritianum and their effects on two cancer cell lines. Int. J. Environ. Res. Public Health 16, 602 (2019).","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"57124_CR35","doi-asserted-by":"publisher","first-page":"e12406","DOI":"10.1016\/j.heliyon.2022.e12406","volume":"8","author":"KI Tapfuma","year":"2022","unstructured":"Tapfuma, K. I. et al. Antimycobacterial activity and molecular docking of methanolic extracts and compounds of marine fungi from Saldanha and False Bays, South Africa. Heliyon 8, e12406 (2022).","journal-title":"Heliyon"},{"key":"57124_CR36","doi-asserted-by":"publisher","first-page":"247","DOI":"10.3390\/antibiotics8040247","volume":"8","author":"KN Venugopala","year":"2019","unstructured":"Venugopala, K. N. et al. Anti-tubercular activity of substituted 7-methyl and 7-formylindolizines and in silico study for prospective molecular target identification. Antibiotics 8, 247 (2019).","journal-title":"Antibiotics"},{"key":"57124_CR37","doi-asserted-by":"publisher","first-page":"4542","DOI":"10.3390\/molecules27144542","volume":"27","author":"SM Abdelrahman","year":"2022","unstructured":"Abdelrahman, S. M., Dosoky, N. S., Hanora, A. M. & Lopanik, N. B. Metabolomic profiling and molecular networking of nudibranch-associated Streptomyces sp. SCSIO 001680. Molecules 27, 4542 (2022).","journal-title":"Molecules"},{"key":"57124_CR38","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3597","author":"M Wang","year":"2016","unstructured":"Wang, M. et al. Sharing and community curation of mass spectrometry data with global natural products social molecular networking. Nat. Biotechnol. https:\/\/doi.org\/10.1038\/nbt.3597 (2016).","journal-title":"Nat. Biotechnol."},{"key":"57124_CR39","doi-asserted-by":"publisher","first-page":"131891","DOI":"10.1016\/j.foodchem.2021.131891","volume":"375","author":"JP da Silva Oliveira","year":"2022","unstructured":"da Silva Oliveira, J. P., Garrett, R., Bello Koblitz, M. G. & Furtado Macedo, A. Vanilla flavor: Species from the Atlantic forest as natural alternatives. Food Chem. 375, 131891 (2022).","journal-title":"Food Chem."},{"key":"57124_CR40","first-page":"1","volume":"8","author":"YS Guo","year":"2018","unstructured":"Guo, Y. S. & Tao, J. Z. Metabolomics and pathway analyses to characterize metabolic alterations in pregnant dairy cows on D 17 and D 45 after AI. Sci. Rep. 8, 1\u20138 (2018).","journal-title":"Sci. Rep."},{"key":"57124_CR41","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26226944","author":"K Zong","year":"2021","unstructured":"Zong, K. et al. Molecules virtual screening and molecular dynamics simulation study of influenza polymerase PB2 inhibitors. Molecules https:\/\/doi.org\/10.3390\/molecules26226944 (2021).","journal-title":"Molecules"},{"key":"57124_CR42","doi-asserted-by":"publisher","first-page":"6177","DOI":"10.1021\/jm051256o","volume":"49","author":"RA Friesner","year":"2006","unstructured":"Friesner, R. A. et al. Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J. Med. Chem. 49, 6177\u20136196 (2006).","journal-title":"J. Med. Chem."},{"key":"57124_CR43","first-page":"280","volume":"5","author":"AK Pandey","year":"2018","unstructured":"Pandey, A. K., Shukla, D. V., Singh, V. & Narayan, V. Structural, IR spectra NBO, TDDFT, AIM calculation, biological activity and docking property of [1,2,4]-triazolo[3,4-b][1,3,4] thiadiazole. EJBAS 5, 280\u2013288 (2018).","journal-title":"EJBAS"},{"key":"57124_CR44","doi-asserted-by":"publisher","first-page":"8569","DOI":"10.3390\/molecules27238569","volume":"27","author":"NJ Gumede","year":"2022","unstructured":"Gumede, N. J. Pathfinder-driven chemical space exploration and multiparameter optimization in tandem with glide\/IFD and QSAR-based active learning approach to prioritize design ideas for FEP+ calculations of SARS-CoV-2 PLpro inhibitors. Molecules 27, 8569 (2022).","journal-title":"Molecules"},{"key":"57124_CR45","doi-asserted-by":"publisher","first-page":"561","DOI":"10.3390\/met8070561","volume":"8","author":"P Fu","year":"2018","unstructured":"Fu, P., Li, Z., Feng, J. & Bian, Z. Recovery of gold and iron from cyanide tailings with a combined direct reduction roasting and leaching process. Metals (Basel) 8, 561 (2018).","journal-title":"Metals (Basel)"},{"key":"57124_CR46","doi-asserted-by":"publisher","first-page":"138052","DOI":"10.1016\/j.chemosphere.2023.138052","volume":"320","author":"L Qian","year":"2023","unstructured":"Qian, L., Lin, H., Li, B. & Dong, Y. Physicochemical characteristics and microbial communities of rhizosphere in complex amendment-assisted soilless revegetation of gold mine tailings. Chemosphere 320, 138052 (2023).","journal-title":"Chemosphere"},{"key":"57124_CR47","doi-asserted-by":"publisher","first-page":"113749","DOI":"10.1016\/j.envres.2022.113749","volume":"214","author":"R Qi","year":"2022","unstructured":"Qi, R. et al. Heavy metal(loid)s shape the soil bacterial community and functional genes of desert grassland in a gold mining area in the semi-arid region. Environ. Res. 214, 113749 (2022).","journal-title":"Environ. Res."},{"key":"57124_CR48","doi-asserted-by":"publisher","first-page":"2785","DOI":"10.3389\/fmicb.2018.02785","volume":"9","author":"TC Santini","year":"2018","unstructured":"Santini, T. C., Raudsepp, M., Hamilton, J. & Nunn, J. Extreme geochemical conditions and dispersal limitation retard primary succession of microbial communities in gold tailings. Front. Microbiol. 9, 2785 (2018).","journal-title":"Front. Microbiol."},{"key":"57124_CR49","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1099\/mic.0.037143-0","volume":"156","author":"GM Gadd","year":"2010","unstructured":"Gadd, G. M. Metals, minerals and microbes: Geomicrobiology and bioremediation. Microbiology 156, 609\u2013643 (2010).","journal-title":"Microbiology"},{"key":"57124_CR50","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.ecoenv.2018.09.011","volume":"165","author":"H Ji","year":"2018","unstructured":"Ji, H., Zhang, Y., Bararunyeretse, P. & Li, H. Characterization of microbial communities of soils from gold mine tailings and identification of mercury-resistant strain. Ecotoxicol. Environ. Saf. 165, 182\u2013193 (2018).","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"57124_CR51","doi-asserted-by":"publisher","first-page":"1579","DOI":"10.1038\/ismej.2014.245","volume":"9","author":"LX Chen","year":"2014","unstructured":"Chen, L. X. et al. Comparative metagenomic and metatranscriptomic analyses of microbial communities in acid mine drainage. ISME J. 9, 1579\u20131592 (2014).","journal-title":"ISME J."},{"key":"57124_CR52","doi-asserted-by":"publisher","first-page":"157","DOI":"10.3390\/antibiotics8040157","volume":"8","author":"HL Robertsen","year":"2019","unstructured":"Robertsen, H. L. & Musiol-Kroll, E. M. Actinomycete-derived polyketides as a source of antibiotics and lead structures for the development of new antimicrobial drugs. Antibiotics 8, 157 (2019).","journal-title":"Antibiotics"},{"key":"57124_CR53","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3390\/antibiotics8030105","volume":"8","author":"Y Mast","year":"2019","unstructured":"Mast, Y. & Stegmann, E. Actinomycetes: The antibiotics producers. Antibiotics 8, 10\u201313 (2019).","journal-title":"Antibiotics"},{"key":"57124_CR54","first-page":"35","volume":"21","author":"BR Mrunalini","year":"2017","unstructured":"Mrunalini, B. R. & Girisha, S. T. Molecular phylogenetic analysis of soil bacteria. Res. J. Chem. Environ. 21, 35\u201341 (2017).","journal-title":"Res. J. Chem. Environ."},{"key":"57124_CR55","doi-asserted-by":"publisher","first-page":"1424","DOI":"10.3389\/fmicb.2019.01424","volume":"10","author":"H Li","year":"2019","unstructured":"Li, H. et al. The diversity and geographic distribution of cultivable bacillus-like bacteria across black soils of Northeast China. Front. Microbiol. 10, 1424 (2019).","journal-title":"Front. Microbiol."},{"key":"57124_CR56","doi-asserted-by":"publisher","first-page":"2943","DOI":"10.1128\/AEM.66.7.2943-2950.2000","volume":"66","author":"J Dunbar","year":"2000","unstructured":"Dunbar, J., Ticknor, L. O., Kuske, C. R. & Icrobiol, A. P. Assessment of microbial diversity in four southwestern united states soils by 16S rRNA gene terminal restriction fragment analysis. Appl. Environ. Microbiol. 66, 2943\u20132950 (2000).","journal-title":"Appl. Environ. Microbiol."},{"key":"57124_CR57","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.01167","author":"J Zhang","year":"2020","unstructured":"Zhang, J. et al. Surfactin like broad spectrum antimicrobial lipopeptide co-produced with sublancin from bacillus subtilis strain A52: Dual reservoir of bioactives. Front. Microbiol. https:\/\/doi.org\/10.3389\/fmicb.2020.01167 (2020).","journal-title":"Front. Microbiol."},{"key":"57124_CR58","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1038\/s41467-022-28668-z","volume":"13","author":"L Xia","year":"2022","unstructured":"Xia, L. et al. Biosynthetic gene cluster profiling predicts the positive association between antagonism and phylogeny in Bacillus. Nat. Commun. 13, 1023 (2022).","journal-title":"Nat. Commun."},{"key":"57124_CR59","doi-asserted-by":"publisher","first-page":"2243","DOI":"10.1021\/acssynbio.1c00154","volume":"10","author":"J Zhu","year":"2021","unstructured":"Zhu, J. et al. Metabolic engineering of aspartic acid supply modules for enhanced production of bacitracin in Bacillus licheniformis. ACS Synth. Biol. 10, 2243\u20132251 (2021).","journal-title":"ACS Synth. Biol."},{"key":"57124_CR60","doi-asserted-by":"publisher","first-page":"456","DOI":"10.3390\/microorganisms11020456","volume":"11","author":"D Mart\u00edn-Gonz\u00e1lez","year":"2023","unstructured":"Mart\u00edn-Gonz\u00e1lez, D., Bordel, S., Solis, S., Gutierrez-Merino, J. & Santos-Beneit, F. Characterization of Bacillus strains from natural honeybee products with high keratinolytic activity and antimicrobial potential. Microorganisms 11, 456 (2023).","journal-title":"Microorganisms"},{"key":"57124_CR61","doi-asserted-by":"publisher","first-page":"2705","DOI":"10.1111\/jam.15397","volume":"132","author":"M Quintero","year":"2022","unstructured":"Quintero, M. et al. In vitro biological activity of extracts from marine bacteria cultures against Toxoplasma gondii and Mycobacterium tuberculosis. J. Appl. Microbiol. 132, 2705\u20132720 (2022).","journal-title":"J. Appl. Microbiol."},{"key":"57124_CR62","doi-asserted-by":"publisher","first-page":"3205","DOI":"10.3390\/plants11233205","volume":"11","author":"H Zhang","year":"2022","unstructured":"Zhang, H. et al. Metabolites from Bacillus subtilis J-15 affect seedling growth of Arabidopsis thaliana and cotton plants. Plants 11, 3205 (2022).","journal-title":"Plants"},{"key":"57124_CR63","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1016\/j.jscs.2011.11.021","volume":"18","author":"NC Desai","year":"2014","unstructured":"Desai, N. C. et al. Green synthesis of novel quinoline based imidazole derivatives and evaluation of their antimicrobial activity. J. Saudi Chem. Soc 18, 963\u2013971 (2014).","journal-title":"J. Saudi Chem. Soc"},{"key":"57124_CR64","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.ejmech.2018.03.016","volume":"150","author":"YL Fan","year":"2018","unstructured":"Fan, Y. L. et al. Recent advances of imidazole-containing derivatives as anti-tubercular agents. Eur. J. Med. Chem. 150, 347\u2013365 (2018).","journal-title":"Eur. J. Med. Chem."},{"key":"57124_CR65","doi-asserted-by":"publisher","first-page":"104538","DOI":"10.1016\/j.bioorg.2020.104538","volume":"107","author":"TM Dhameliya","year":"2021","unstructured":"Dhameliya, T. M. et al. Design, synthesis, and biological evaluation of benzo[d]imidazole-2-carboxamides as new anti-TB agents. Bioorg. Chem. 107, 104538 (2021).","journal-title":"Bioorg. Chem."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-57124-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-57124-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-57124-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T08:11:55Z","timestamp":1711008715000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-57124-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,21]]},"references-count":65,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["57124"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-57124-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,21]]},"assertion":[{"value":"16 December 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 March 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 March 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"6794"}}