{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T15:51:52Z","timestamp":1784389912174,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1008284","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T00:00:00Z","timestamp":1612828800000}}],"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T00:00:00Z","timestamp":1611792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["MCB 1818297"],"award-info":[{"award-number":["MCB 1818297"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["MCB 1818297"],"award-info":[{"award-number":["MCB 1818297"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NSF EPSCoR Center for Root and Rhizobiome Innovation","award":["Grant 25-1215-0139-025"],"award-info":[{"award-number":["Grant 25-1215-0139-025"]}]},{"name":"NSF EPSCoR Center for Root and Rhizobiome Innovation","award":["Grant 25-1215-0139-025"],"award-info":[{"award-number":["Grant 25-1215-0139-025"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Sphingolipids are a vital component of plant cellular endomembranes and carry out multiple functional and regulatory roles. Different sphingolipid species confer rigidity to the membrane structure, facilitate trafficking of secretory proteins, and initiate programmed cell death. Although the regulation of the sphingolipid pathway is yet to be uncovered, increasing evidence has pointed to orosomucoid proteins (ORMs) playing a major regulatory role and potentially interacting with a number of components in the pathway, including both enzymes and sphingolipids. However, experimental exploration of new regulatory interactions is time consuming and often infeasible. In this work, a computational approach was taken to address this challenge. A metabolic network of the sphingolipid pathway in plants was reconstructed. The steady-state rates of reactions in the network were then determined through measurements of growth and cellular composition of the different sphingolipids in Arabidopsis seedlings. The Ensemble modeling framework was modified to accurately account for activation mechanisms and subsequently used to generate sets of kinetic parameters that converge to the measured steady-state fluxes in a thermodynamically consistent manner. In addition, the framework was appended with an additional module to automate screening the parameters and to output models consistent with previously reported network responses to different perturbations. By analyzing the network\u2019s response in the presence of different combinations of regulatory mechanisms, the model captured the experimentally observed repressive effect of ORMs on serine palmitoyltransferase (SPT). Furthermore, predictions point to a second regulatory role of ORM proteins, namely as an activator of class II (or LOH1 and LOH3) ceramide synthases. This activating role was found to be modulated by the concentration of free ceramides, where an accumulation of these sphingolipid species dampened the activating effect of ORMs on ceramide synthase. The predictions pave the way for future guided experiments and have implications in engineering crops with higher biotic stress tolerance.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1008284","type":"journal-article","created":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T14:46:16Z","timestamp":1611845176000},"page":"e1008284","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Dissecting the regulatory roles of ORM proteins in the sphingolipid pathway of plants"],"prefix":"10.1371","volume":"17","author":[{"given":"Adil","family":"Alsiyabi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4779-7729","authenticated-orcid":true,"given":"Ariadna 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