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Biosynthesis and Structure Activity Relationship Investigations of the Diazeniumdiolate Antifungal Agent Fragin


Sieber, Simon; Daeppen, Christophe; Jenul, Christian; Mannancherril, Vidya; Eberl, Leo; Gademann, Karl (2020). Biosynthesis and Structure Activity Relationship Investigations of the Diazeniumdiolate Antifungal Agent Fragin. Chembiochem, 21(11):1587-1592.

Abstract

Only a few natural products possessing a diazeniumdiolate have been isolated and usually these compounds display a broad range of biological activities. Only recently the first diazeniumdiolate natural product biosynthetic gene cluster was identified in Burkholderia cenocepacia H111, which produces the fungicide (-)-fragin and the signal molecule (rac)-valdiazen. In this study, L-valine was identified as the initial substrate of (-)-fragin biosynthesis by feeding experiments using isotopically labeled amino acids. The formation of the diazeniumdiolate was chemically studied by several proposed intermediates. Our results indicate that the functional group is formed during an early stage of the biosynthesis. Furthermore, an oxime compound was identified as a degradation product of (-)-fragin and was also observed in the crude extract of the wild type strain. Moreover, structure-activity relationship analysis revealed that each moiety of (-)-fragin is essential for its biological activity.

Abstract

Only a few natural products possessing a diazeniumdiolate have been isolated and usually these compounds display a broad range of biological activities. Only recently the first diazeniumdiolate natural product biosynthetic gene cluster was identified in Burkholderia cenocepacia H111, which produces the fungicide (-)-fragin and the signal molecule (rac)-valdiazen. In this study, L-valine was identified as the initial substrate of (-)-fragin biosynthesis by feeding experiments using isotopically labeled amino acids. The formation of the diazeniumdiolate was chemically studied by several proposed intermediates. Our results indicate that the functional group is formed during an early stage of the biosynthesis. Furthermore, an oxime compound was identified as a degradation product of (-)-fragin and was also observed in the crude extract of the wild type strain. Moreover, structure-activity relationship analysis revealed that each moiety of (-)-fragin is essential for its biological activity.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
07 Faculty of Science > Department of Plant and Microbial Biology
Dewey Decimal Classification:580 Plants (Botany)
Scopus Subject Areas:Life Sciences > Biochemistry
Life Sciences > Molecular Medicine
Life Sciences > Molecular Biology
Physical Sciences > Organic Chemistry
Language:English
Date:2 June 2020
Deposited On:21 Feb 2020 13:29
Last Modified:25 Feb 2021 08:24
Publisher:Wiley-VCH Verlag
ISSN:1439-4227
OA Status:Green
Publisher DOI:https://doi.org/10.1002/cbic.201900755
PubMed ID:31945256

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