Biosynthesis and Structure-Activity Relationship Investigations of the Diazeniumdiolate Antifungal Agent Fragin.
Chembiochem
; 21(11): 1587-1592, 2020 06 02.
Article
en En
| MEDLINE
| ID: mdl-31945256
ABSTRACT
Only a few natural products incorporating a diazeniumdiolate moiety have been isolated, and these compounds usually display a broad range of biological activities. Only recently has the first diazeniumdiolate natural product biosynthetic gene cluster been 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 with the aid of feeding experiments using isotopically labelled amino acid. The formation of the diazeniumdiolate was chemically studied with 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, a structure-activity relationship analysis revealed that each moiety of (-)-fragin is essential for its biological activity.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oxidorreductasas
/
Compuestos Azo
/
Proteínas Bacterianas
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Productos Biológicos
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Genoma Bacteriano
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Burkholderia cenocepacia
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Antifúngicos
Idioma:
En
Revista:
Chembiochem
Asunto de la revista:
BIOQUIMICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Suiza