Acetobixan, an inhibitor of cellulose synthesis identified by microbial bioprospecting
In plants, cellulose biosynthesis is an essential process for anisotropic growth and therefore is an ideal target for inhibition. Based on the documented utility of small-molecule inhibitors to dissect complex cellular processes we identified a cellulose biosynthesis inhibitor (CBI), named acetobixa...
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| Veröffentlicht in: | PloS one 2014-04, Vol.9 (4), p.e95245-e95245 |
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| creator | Xia, Ye Lei, Lei Brabham, Chad Stork, Jozsef Strickland, James Ladak, Adam Gu, Ying Wallace, Ian DeBolt, Seth |
| description | In plants, cellulose biosynthesis is an essential process for anisotropic growth and therefore is an ideal target for inhibition. Based on the documented utility of small-molecule inhibitors to dissect complex cellular processes we identified a cellulose biosynthesis inhibitor (CBI), named acetobixan, by bio-prospecting among compounds secreted by endophytic microorganisms. Acetobixan was identified using a drug-gene interaction screen to sift through hundreds of endophytic microbial secretions for one that caused synergistic reduction in root expansion of the leaky AtcesA6prc1-1 mutant. We then mined this microbial secretion for compounds that were differentially abundant compared with Bacilli that failed to mimic CBI action to isolate a lead pharmacophore. Analogs of this lead compound were screened for CBI activity, and the most potent analog was named acetobixan. In living Arabidopsis cells visualized by confocal microscopy, acetobixan treatment caused CESA particles localized at the plasma membrane (PM) to rapidly re-localize to cytoplasmic vesicles. Acetobixan inhibited 14C-Glc uptake into crystalline cellulose. Moreover, cortical microtubule dynamics were not disrupted by acetobixan, suggesting specific activity towards cellulose synthesis. Previous CBI resistant mutants such as ixr1-2, ixr2-1 or aegeus were not cross resistant to acetobixan indicating that acetobixan targets a different aspect of cellulose biosynthesis. |
| doi_str_mv | 10.1371/journal.pone.0095245 |
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Based on the documented utility of small-molecule inhibitors to dissect complex cellular processes we identified a cellulose biosynthesis inhibitor (CBI), named acetobixan, by bio-prospecting among compounds secreted by endophytic microorganisms. Acetobixan was identified using a drug-gene interaction screen to sift through hundreds of endophytic microbial secretions for one that caused synergistic reduction in root expansion of the leaky AtcesA6prc1-1 mutant. We then mined this microbial secretion for compounds that were differentially abundant compared with Bacilli that failed to mimic CBI action to isolate a lead pharmacophore. Analogs of this lead compound were screened for CBI activity, and the most potent analog was named acetobixan. In living Arabidopsis cells visualized by confocal microscopy, acetobixan treatment caused CESA particles localized at the plasma membrane (PM) to rapidly re-localize to cytoplasmic vesicles. Acetobixan inhibited 14C-Glc uptake into crystalline cellulose. Moreover, cortical microtubule dynamics were not disrupted by acetobixan, suggesting specific activity towards cellulose synthesis. Previous CBI resistant mutants such as ixr1-2, ixr2-1 or aegeus were not cross resistant to acetobixan indicating that acetobixan targets a different aspect of cellulose biosynthesis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0095245</identifier><identifier>PMID: 24748166</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acetamides - pharmacology ; Analogs ; Arabidopsis ; Arabidopsis thaliana ; Bacilli ; Bacillus ; Base Sequence ; Biochemistry ; Biology and Life Sciences ; Bioprospecting ; Biosynthesis ; cell membranes ; Cellulose ; Cellulose - biosynthesis ; Chromatography, Liquid ; computer software ; Confocal ; Confocal microscopy ; Cortex ; Crystalline cellulose ; Deoxyribonucleic acid ; DNA ; DNA Primers ; E coli ; Ecology and Environmental Sciences ; Endophytes ; ENVIRONMENTAL SCIENCES ; Escherichia coli ; Genomes ; Horticulture ; Inhibition ; Inhibitors ; Mass Spectrometry ; Metabolism ; Metabolites ; Microbiology ; Microorganisms ; Microscopy ; Microscopy, Confocal ; Molecular biology ; Mutants ; Mutation ; Pharmacology ; Physiological aspects ; Physiology ; Plants (botany) ; Plasma ; Prospecting ; R&D ; Research & development ; Resistant mutant ; RNA, Ribosomal, 16S - genetics ; Secretion ; Secretions ; seedlings ; Signal transduction ; small molecules</subject><ispartof>PloS one, 2014-04, Vol.9 (4), p.e95245-e95245</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Xia et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Based on the documented utility of small-molecule inhibitors to dissect complex cellular processes we identified a cellulose biosynthesis inhibitor (CBI), named acetobixan, by bio-prospecting among compounds secreted by endophytic microorganisms. Acetobixan was identified using a drug-gene interaction screen to sift through hundreds of endophytic microbial secretions for one that caused synergistic reduction in root expansion of the leaky AtcesA6prc1-1 mutant. We then mined this microbial secretion for compounds that were differentially abundant compared with Bacilli that failed to mimic CBI action to isolate a lead pharmacophore. Analogs of this lead compound were screened for CBI activity, and the most potent analog was named acetobixan. In living Arabidopsis cells visualized by confocal microscopy, acetobixan treatment caused CESA particles localized at the plasma membrane (PM) to rapidly re-localize to cytoplasmic vesicles. 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Based on the documented utility of small-molecule inhibitors to dissect complex cellular processes we identified a cellulose biosynthesis inhibitor (CBI), named acetobixan, by bio-prospecting among compounds secreted by endophytic microorganisms. Acetobixan was identified using a drug-gene interaction screen to sift through hundreds of endophytic microbial secretions for one that caused synergistic reduction in root expansion of the leaky AtcesA6prc1-1 mutant. We then mined this microbial secretion for compounds that were differentially abundant compared with Bacilli that failed to mimic CBI action to isolate a lead pharmacophore. Analogs of this lead compound were screened for CBI activity, and the most potent analog was named acetobixan. In living Arabidopsis cells visualized by confocal microscopy, acetobixan treatment caused CESA particles localized at the plasma membrane (PM) to rapidly re-localize to cytoplasmic vesicles. Acetobixan inhibited 14C-Glc uptake into crystalline cellulose. Moreover, cortical microtubule dynamics were not disrupted by acetobixan, suggesting specific activity towards cellulose synthesis. Previous CBI resistant mutants such as ixr1-2, ixr2-1 or aegeus were not cross resistant to acetobixan indicating that acetobixan targets a different aspect of cellulose biosynthesis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24748166</pmid><doi>10.1371/journal.pone.0095245</doi><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-04, Vol.9 (4), p.e95245-e95245 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1517611126 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Acetamides - pharmacology Analogs Arabidopsis Arabidopsis thaliana Bacilli Bacillus Base Sequence Biochemistry Biology and Life Sciences Bioprospecting Biosynthesis cell membranes Cellulose Cellulose - biosynthesis Chromatography, Liquid computer software Confocal Confocal microscopy Cortex Crystalline cellulose Deoxyribonucleic acid DNA DNA Primers E coli Ecology and Environmental Sciences Endophytes ENVIRONMENTAL SCIENCES Escherichia coli Genomes Horticulture Inhibition Inhibitors Mass Spectrometry Metabolism Metabolites Microbiology Microorganisms Microscopy Microscopy, Confocal Molecular biology Mutants Mutation Pharmacology Physiological aspects Physiology Plants (botany) Plasma Prospecting R&D Research & development Resistant mutant RNA, Ribosomal, 16S - genetics Secretion Secretions seedlings Signal transduction small molecules |
| title | Acetobixan, an inhibitor of cellulose synthesis identified by microbial bioprospecting |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-15T20%3A41%3A29IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Acetobixan,%20an%20inhibitor%20of%20cellulose%20synthesis%20identified%20by%20microbial%20bioprospecting&rft.jtitle=PloS%20one&rft.au=Xia,%20Ye&rft.aucorp=Univ.%20of%20Kentucky,%20Lexington,%20KY%20(United%20States)&rft.date=2014-04-01&rft.volume=9&rft.issue=4&rft.spage=e95245&rft.epage=e95245&rft.pages=e95245-e95245&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0095245&rft_dat=%3Cgale_plos_%3EA375584609%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1517611126&rft_id=info:pmid/24748166&rft_galeid=A375584609&rft_doaj_id=oai_doaj_org_article_c1537edefa0940c38cc52e0237e9b970&rfr_iscdi=true |