Isolation and Identification of <i>Cis-</i>2,5-Diketopiperazine from a Novel <i>Bacillus</i> Strain and Synthesis of Its Four Stereoisomers

The <i>Bacillus horneckiae</i>-like strain 2011SOCCUF3 was isolated from the marine sponge <i>Spongia officinalis</i> and its metabolome was studied for secondary metabolites with antimicrobial activity. Culturing in the presence of Diaion HP-20 resin and purifying the cultur...

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Main Authors: Alan M. C. Obled, Refaat B. Hamed, Edward Spence, Marija K. Zacharova, Sunil V. Sharma, Yunpeng Wang, Rosemary Lynch, Helen Connaris, Adina Tatheer, Marie-Lise Bourguet-Kondracki, Gordon J. Florence, Rebecca J. M. Goss
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Language:English
Published: MDPI AG 2025-05-01
Series:Marine Drugs
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Online Access:https://www.mdpi.com/1660-3397/23/6/234
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author Alan M. C. Obled
Refaat B. Hamed
Edward Spence
Marija K. Zacharova
Sunil V. Sharma
Yunpeng Wang
Rosemary Lynch
Helen Connaris
Adina Tatheer
Marie-Lise Bourguet-Kondracki
Gordon J. Florence
Rebecca J. M. Goss
author_facet Alan M. C. Obled
Refaat B. Hamed
Edward Spence
Marija K. Zacharova
Sunil V. Sharma
Yunpeng Wang
Rosemary Lynch
Helen Connaris
Adina Tatheer
Marie-Lise Bourguet-Kondracki
Gordon J. Florence
Rebecca J. M. Goss
author_sort Alan M. C. Obled
collection DOAJ
description The <i>Bacillus horneckiae</i>-like strain 2011SOCCUF3 was isolated from the marine sponge <i>Spongia officinalis</i> and its metabolome was studied for secondary metabolites with antimicrobial activity. Culturing in the presence of Diaion HP-20 resin and purifying the culture extract identified cyclo-phenylalanine-proline (cyclo-(Phe-Pro)), a 2,5-diketopiperazine (2,5-DKP), isolated as a major metabolite. Further, LCMS analysis of the extract showed the presence of two isomers of the molecule in the culture broth. To confirm the stereochemistry of the isomers observed in the natural extract, all four stereoisomers of cyclo-(Phe-Pro) were synthesised. NMR and LCMS studies identified the presence of both <i>cis-</i> and <i>trans</i>-cyclo-(Phe-Pro) isomers. Stability and epimerisation studies on synthetic isomers and the effect of culturing conditions suggested that the less stable <i>cis</i> isomer was naturally produced, which epimerised in culture broth.
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spelling doaj-art-e1e10e64a54b4bb4a23ec616dcc96a022025-08-20T03:27:37ZengMDPI AGMarine Drugs1660-33972025-05-0123623410.3390/md23060234Isolation and Identification of <i>Cis-</i>2,5-Diketopiperazine from a Novel <i>Bacillus</i> Strain and Synthesis of Its Four StereoisomersAlan M. C. Obled0Refaat B. Hamed1Edward Spence2Marija K. Zacharova3Sunil V. Sharma4Yunpeng Wang5Rosemary Lynch6Helen Connaris7Adina Tatheer8Marie-Lise Bourguet-Kondracki9Gordon J. Florence10Rebecca J. M. Goss11School of Chemistry & BSRC, and Integrated Institute of Engineering, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UKSchool of Chemistry & BSRC, and Integrated Institute of Engineering, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UKSchool of Chemistry & BSRC, and Integrated Institute of Engineering, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UKSchool of Chemistry & BSRC, and Integrated Institute of Engineering, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UKSchool of Chemistry & BSRC, and Integrated Institute of Engineering, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UKSchool of Chemistry & BSRC, and Integrated Institute of Engineering, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UKSchool of Chemistry & BSRC, and Integrated Institute of Engineering, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UKSchool of Chemistry & BSRC, and Integrated Institute of Engineering, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UKSchool of Chemistry & BSRC, and Integrated Institute of Engineering, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UKLaboratoire Molécules de Communication et Adaptation des Micro-Organismes, UMR 7245 CNRS, Muséum National d’Histoire Naturelle, 57 Rue Cuvier (C.P. 54), 75005 Paris, FranceSchool of Chemistry & BSRC, and Integrated Institute of Engineering, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UKSchool of Chemistry & BSRC, and Integrated Institute of Engineering, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UKThe <i>Bacillus horneckiae</i>-like strain 2011SOCCUF3 was isolated from the marine sponge <i>Spongia officinalis</i> and its metabolome was studied for secondary metabolites with antimicrobial activity. Culturing in the presence of Diaion HP-20 resin and purifying the culture extract identified cyclo-phenylalanine-proline (cyclo-(Phe-Pro)), a 2,5-diketopiperazine (2,5-DKP), isolated as a major metabolite. Further, LCMS analysis of the extract showed the presence of two isomers of the molecule in the culture broth. To confirm the stereochemistry of the isomers observed in the natural extract, all four stereoisomers of cyclo-(Phe-Pro) were synthesised. NMR and LCMS studies identified the presence of both <i>cis-</i> and <i>trans</i>-cyclo-(Phe-Pro) isomers. Stability and epimerisation studies on synthetic isomers and the effect of culturing conditions suggested that the less stable <i>cis</i> isomer was naturally produced, which epimerised in culture broth.https://www.mdpi.com/1660-3397/23/6/234<i>Bacillus</i>marine sponge bacteriadiketopiperazinecyclopeptideantimicrobial
spellingShingle Alan M. C. Obled
Refaat B. Hamed
Edward Spence
Marija K. Zacharova
Sunil V. Sharma
Yunpeng Wang
Rosemary Lynch
Helen Connaris
Adina Tatheer
Marie-Lise Bourguet-Kondracki
Gordon J. Florence
Rebecca J. M. Goss
Isolation and Identification of <i>Cis-</i>2,5-Diketopiperazine from a Novel <i>Bacillus</i> Strain and Synthesis of Its Four Stereoisomers
Marine Drugs
<i>Bacillus</i>
marine sponge bacteria
diketopiperazine
cyclopeptide
antimicrobial
title Isolation and Identification of <i>Cis-</i>2,5-Diketopiperazine from a Novel <i>Bacillus</i> Strain and Synthesis of Its Four Stereoisomers
title_full Isolation and Identification of <i>Cis-</i>2,5-Diketopiperazine from a Novel <i>Bacillus</i> Strain and Synthesis of Its Four Stereoisomers
title_fullStr Isolation and Identification of <i>Cis-</i>2,5-Diketopiperazine from a Novel <i>Bacillus</i> Strain and Synthesis of Its Four Stereoisomers
title_full_unstemmed Isolation and Identification of <i>Cis-</i>2,5-Diketopiperazine from a Novel <i>Bacillus</i> Strain and Synthesis of Its Four Stereoisomers
title_short Isolation and Identification of <i>Cis-</i>2,5-Diketopiperazine from a Novel <i>Bacillus</i> Strain and Synthesis of Its Four Stereoisomers
title_sort isolation and identification of i cis i 2 5 diketopiperazine from a novel i bacillus i strain and synthesis of its four stereoisomers
topic <i>Bacillus</i>
marine sponge bacteria
diketopiperazine
cyclopeptide
antimicrobial
url https://www.mdpi.com/1660-3397/23/6/234
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