Anti-cryptococcal activity of preussolides A and B, phosphoethanolamine-substituted 24-membered macrolides, and leptosin C from coprophilous isolates of Preussia typharum.
J Ind Microbiol Biotechnol
; 48(9-10)2021 Dec 23.
Article
en En
| MEDLINE
| ID: mdl-33640980
ABSTRACT
Cryptococcus neoformans is a serious human pathogen with limited options for treatment. We have interrogated extracts from fungal fermentations to find Cryptococcus-inhibiting natural products using assays for growth inhibition and differential thermosensitivity. Extracts from fermentations of four fungal strains from wild and domestic animal dung from Arkansas and West Virginia, USA were identified as Preussia typharum. The extracts exhibited two antifungal regions. Purification of one region yielded new 24-carbon macrolides incorporating both a phosphoethanolamine unit and a bridging tetrahydrofuran ring. The structures of these metabolites were established mainly by analysis of high-resolution mass spectrometry and 2D NMR data. Relative configurations were assigned using NOESY data, and the structure assignments were supported by NMR comparison with similar compounds. These new metabolites are designated preussolides A and B. The second active region was caused by the cytotoxin, leptosin C. Genome sequencing of the four strains revealed biosynthetic gene clusters consistent with those known to encode phosphoethanolamine-bearing polyketide macrolides and the biosynthesis of dimeric epipolythiodioxopiperazines. All three compounds showed moderate to potent and selective antifungal activity toward the pathogenic yeast C. neoformans.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Macrólidos
/
Cryptococcus neoformans
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Ind Microbiol Biotechnol
Asunto de la revista:
BIOTECNOLOGIA
/
MICROBIOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos