{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:05:45Z","timestamp":1789153545199,"version":"build-2803163510"},"reference-count":84,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T00:00:00Z","timestamp":1636502400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010801","name":"Xunta de Galicia","doi-asserted-by":"publisher","award":["ED431E 2018\/07"],"award-info":[{"award-number":["ED431E 2018\/07"]}],"id":[{"id":"10.13039\/501100010801","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Phenolic compounds constitute an important family of natural bioactive compounds responsible for the medicinal properties attributed to Bryophyllum plants (genus Kalanchoe, Crassulaceae), but their production by these medicinal plants has not been characterized to date. In this work, a combinatorial approach including plant tissue culture, untargeted metabolomics, and machine learning is proposed to unravel the critical factors behind the biosynthesis of phenolic compounds in these species. The untargeted metabolomics revealed 485 annotated compounds that were produced by three Bryophyllum species cultured in vitro in a genotype and organ-dependent manner. Neurofuzzy logic (NFL) predictive models assessed the significant influence of genotypes and organs and identified the key nutrients from culture media formulations involved in phenolic compound biosynthesis. Sulfate played a critical role in tyrosol and lignan biosynthesis, copper in phenolic acid biosynthesis, calcium in stilbene biosynthesis, and magnesium in flavanol biosynthesis. Flavonol and anthocyanin biosynthesis was not significantly affected by mineral components. As a result, a predictive biosynthetic model for all the Bryophyllum genotypes was proposed. The combination of untargeted metabolomics with machine learning provided a robust approach to achieve the phytochemical characterization of the previously unexplored species belonging to the Bryophyllum subgenus, facilitating their biotechnological exploitation as a promising source of bioactive compounds.<\/jats:p>","DOI":"10.3390\/plants10112430","type":"journal-article","created":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T23:04:46Z","timestamp":1636671886000},"page":"2430","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["The Combination of Untargeted Metabolomics and Machine Learning Predicts the Biosynthesis of Phenolic Compounds in Bryophyllum Medicinal Plants (Genus Kalanchoe)"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1798-6235","authenticated-orcid":false,"given":"Pascual","family":"Garc\u00eda-P\u00e9rez","sequence":"first","affiliation":[{"name":"Agrobiotech for Health Group, Plant Biology and Soil Science Department, Biology Faculty, University of Vigo, E-36310 Vigo, Spain"},{"name":"CITACA\u2014Agri-Food Research and Transfer Cluster, University of Vigo, E-32004 Ourense, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9278-0459","authenticated-orcid":false,"given":"Leilei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department for Sustainable Food Process, Universit\u00e0 Cattolica del Sacro Cuore, Via Emilia Parmense 84, 29122 Piacenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bego\u00f1a","family":"Miras-Moreno","sequence":"additional","affiliation":[{"name":"Department for Sustainable Food Process, Universit\u00e0 Cattolica del Sacro Cuore, Via Emilia Parmense 84, 29122 Piacenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Lozano-Milo","sequence":"additional","affiliation":[{"name":"Agrobiotech for Health Group, Plant Biology and Soil Science Department, Biology Faculty, University of Vigo, E-36310 Vigo, Spain"},{"name":"CITACA\u2014Agri-Food Research and Transfer Cluster, University of Vigo, E-32004 Ourense, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2835-8958","authenticated-orcid":false,"given":"Mariana","family":"Landin","sequence":"additional","affiliation":[{"name":"I+D Farma Group (GI-1645), Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidade de Santiago de Compostela, E-15782 Santiago de Compostela, Spain"},{"name":"Health Research Institute of Santiago de Compostela (IDIS), E-15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5133-9464","authenticated-orcid":false,"given":"Luigi","family":"Lucini","sequence":"additional","affiliation":[{"name":"Department for Sustainable Food Process, Universit\u00e0 Cattolica del Sacro Cuore, Via Emilia Parmense 84, 29122 Piacenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4622-1728","authenticated-orcid":false,"given":"Pedro P.","family":"Gallego","sequence":"additional","affiliation":[{"name":"Agrobiotech for Health Group, Plant Biology and Soil Science Department, Biology Faculty, University of Vigo, E-36310 Vigo, Spain"},{"name":"CITACA\u2014Agri-Food Research and Transfer Cluster, University of Vigo, E-32004 Ourense, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/B978-0-444-64183-0.00002-6","article-title":"Bioactive Natural Products from the Genus Kalanchoe as Cancer Chemopreventive Agents: A Review","volume":"Volume 61","author":"Rahman","year":"2019","journal-title":"Studies in Natural Products Chemistry"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-P\u00e9rez, P., Lozano-Milo, E., Landin, M., and Gallego, P.P. 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