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      Natural Sources and Bioactivities of 2,4-Di-Tert-Butylphenol and Its Analogs

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          Abstract

          2,4-Di-tert-butylphenol or 2,4-bis(1,1-dimethylethyl)-phenol (2,4-DTBP) is a common toxic secondary metabolite produced by various groups of organisms. The biosources and bioactivities of 2,4-DTBP have been well investigated, but the phenol has not been systematically reviewed. This article provides a comprehensive review of 2,4-DTBP and its analogs with emphasis on natural sources and bioactivities. 2,4-DTBP has been found in at least 169 species of bacteria (16 species, 10 families), fungi (11 species, eight families), diatom (one species, one family), liverwort (one species, one family), pteridiphyta (two species, two families), gymnosperms (four species, one family), dicots (107 species, 58 families), monocots (22 species, eight families), and animals (five species, five families). 2,4-DTBP is often a major component of violate or essential oils and it exhibits potent toxicity against almost all testing organisms, including the producers; however, it is not clear why organisms produce autotoxic 2,4-DTBP and its analogs. The accumulating evidence indicates that the endocidal regulation seems to be the primary function of the phenols in the producing organisms.

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          2,4-Di-tert-butyl phenol as the antifungal, antioxidant bioactive purified from a newly isolated Lactococcus sp.

          The volatile organic compound 2,4-di-tert-butyl phenol (2,4 DTBP) was purified from the cell free supernatant of a newly isolated Lactococcus sp. by solvent extraction and chromatographic techniques. Molecular characterization of the compound by ESI-MS, (1)H NMR and FTIR analysis revealed the structure, C14H22O. Fungicidal activity was demonstrated against Aspergillus niger, Fusarium oxysporum and Penicillium chrysogenum by disc diffusion assay. Among the cell lines tested for cytotoxicity of this compound (normal cell line H9c2 and cancer cell lines HeLa and MCF-7), a remarkable cytotoxicity against HeLa cells with an IC50 value of 10 μg/mL was shown. A biocontrol experiment with 2,4 DTBP supplemented fraction prevented growth of the abovementioned fungi on wheat grains. The study further strengthens the case for development of biopreservatives and dietary antioxidants from lactic acid bacteria for food applications.
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            The volatile-producing Flavobacterium johnsoniae strain GSE09 shows biocontrol activity against Phytophthora capsici in pepper.

            Previously, we selected a bacterial strain (GSE09) antagonistic to Phytophthora capsici on pepper, which produced a volatile compound (2,4-di-tert-butylphenol), inhibiting the pathogen. In this study, we identified strain GSE09 and characterized some of the biological traits of this strain in relation to its antagonistic properties against P. capsici. In addition, we examined bacterial colonization on the root surface or in rhizosphere soil and the effect of various concentrations of the volatile compound and strain GSE09 on pathogen development and radicle infection as well as radicle growth.  Strain GSE09 was identified as Flavobacterium johnsoniae, which forms biofilms and produces indolic compounds and biosurfactant but not hydrogen cyanide (HCN) with little or low levels of antifungal activity and swimming and swarming activities. Fl. johnsoniae GSE09 effectively colonized on pepper root, rhizosphere, and bulk (pot) soil, which reduced the pathogen colonization in the roots and disease severity in the plants. Various concentrations of 2,4-di-tert-butylphenol or strain GSE09 inhibited pathogen development (mycelial growth, sporulation, and zoospore germination) in I-plate (a plastic plate containing a center partition). In addition, germinated seeds treated with the compound (1-100 μg ml⁻¹) or the strain (10²-10¹⁰ cells ml⁻¹) significantly reduced radicle infection by P. capsici without radicle growth inhibition.  These results indicate that colonization of pepper root and rhizosphere by the Fl. johnsoniae strain GSE09, which can form biofilms and produce indolic compounds, biosurfactant, and 2,4-di-tert-butylphenol, might provide effective biocontrol activity against P. capsici.  To our knowledge, this is the first study demonstrating that the Fl. johnsoniae strain GSE09, as a potential biocontrol agent, can effectively protect pepper plants against P. capsici infection by colonizing the roots. © 2012 The Authors Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.
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              Phenol, 2,4-bis(1,1-dimethylethyl) of marine bacterial origin inhibits quorum sensing mediated biofilm formation in the uropathogen Serratia marcescens.

              Intercellular communication in bacteria (quorum sensing, QS) is an important phenomenon in disease dissemination and pathogenesis, which controls biofilm formation also. This study reports the anti-QS and anti-biofilm efficacy of seaweed Gracilaria gracilis associated Vibrio alginolyticus G16 against Serratia marcescens. Purification and mass spectrometric analysis revealed the active principle as phenol, 2,4-bis(1,1-dimethylethyl) [PD]. PD affected the QS regulated virulence factor production in S. marcescens and resulted in a significant (p < 0.05) reduction in biofilm (85%), protease (41.9%), haemolysin (69.9%), lipase (84.3%), prodigiosin (84.5%) and extracellular polysaccharide (84.62%) secretion without hampering growth, as evidenced by XTT [2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] assay. qPCR analysis confirmed the down-regulation of the fimA, fimC, flhD and bsmA genes involved in biofilm formation. Apart from biofilm inhibition and disruption, PD increased the susceptibility of S. marcescens to gentamicin when administered synergistically, which opens another avenue for combinatorial therapy where PD can be used to enhance the efficacy of conventional antibiotics.
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                Author and article information

                Journal
                Toxins (Basel)
                Toxins (Basel)
                toxins
                Toxins
                MDPI
                2072-6651
                06 January 2020
                January 2020
                : 12
                : 1
                : 35
                Affiliations
                [1 ]College of Life Science and Bioengineering, Shenyang University, Shenyang 110044, Liaoning, China; zhaofuqiang@ 123456iae.ac.cn
                [2 ]CAS Key Laboratory of Forest Ecology and Management, Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110016, Liaoning, China
                [3 ]National Center for Pharmaceutical Crops, Arthur Temple College of Forestry and Agriculture, Stephen F. Austin State University, Nacogdoches, TX 75962, USA fuq_zhao@ 123456126.com (Z.S.)
                [4 ]Southern Research Station, USDA Forest Service, 320 Green Street, Athens, GA 30602, USA; rima.lucardi@ 123456usda.gov
                Author notes
                [* ]Correspondence: lis@ 123456sfasu.edu
                Author information
                https://orcid.org/0000-0002-8851-2494
                https://orcid.org/0000-0001-9553-9794
                Article
                toxins-12-00035
                10.3390/toxins12010035
                7020479
                31935944
                1fa9c182-88c6-4726-8113-1dd29c5597a1
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 08 October 2019
                : 16 December 2019
                Categories
                Review

                Molecular medicine
                2,4-di-tert-butylphenol,2,4-bis(1,1-dimethylethyl)-phenol (2,4-dtbp),2,4-dtbp,analogs,natural source,bioactivities,autotoxicity,bacteria,fungi,plants,animals

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