Journal article
Anti-cryptococcal activity of preussolides A and B, phosphoethanolamine-substituted 24-membered macrolides, and leptosin C from coprophilous isolates of Preussia typharum
Journal of industrial microbiology & biotechnology, Vol.48(9-10), kuab022
12/23/2021
DOI: 10.1093/jimb/kuab022
PMCID: PMC8788809
PMID: 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.
Details
- Title: Subtitle
- Anti-cryptococcal activity of preussolides A and B, phosphoethanolamine-substituted 24-membered macrolides, and leptosin C from coprophilous isolates of Preussia typharum
- Creators
- Bruno Perlatti - Texas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77054, USANan Lan - Texas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77054, USAMeichun Xiang - State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, No. 3 Park 1, Beichen West Road, Chaoyang District, Beijing 100101, ChinaCody E Earp - Department of Chemistry, University of Iowa, Iowa City, IA 52242, USAJoseph E Spraker - Hexagon Bio, Menlo Park, CA 94025, USAColin J B Harvey - Hexagon Bio, Menlo Park, CA 94025, USAConnie B Nichols - Departments of Medicine and Molecular Genetics & Microbiology, Duke University Medical Center, Durham, NC 27710, USAJ Andrew Alspaugh - Departments of Medicine and Molecular Genetics & Microbiology, Duke University Medical Center, Durham, NC 27710, USAJames B Gloer - Department of Chemistry, University of Iowa, Iowa City, IA 52242, USAGerald F Bills - Texas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77054, USA
- Resource Type
- Journal article
- Publication Details
- Journal of industrial microbiology & biotechnology, Vol.48(9-10), kuab022
- DOI
- 10.1093/jimb/kuab022
- PMID
- 33640980
- PMCID
- PMC8788809
- ISSN
- 1367-5435
- eISSN
- 1476-5535
- Grant note
- R01 GM121458 / NIGMS NIH HHS Kay and Ben Fortson Endowment Chinese Scholarship Council R01 GM121458 / NIH HHS
- Language
- English
- Date published
- 12/23/2021
- Academic Unit
- Chemistry
- Record Identifier
- 9984216583202771
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