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Biosynthesis of Deoxyamphotericins and Deoxyamphoteronolides by Engineered Strains of Streptomyces nodosus
Date Issued
2003-12-19
Date Available
2019-04-18T09:18:08Z
Abstract
Amphotericin B is an antifungal antibiotic produced by Streptomyces nodosus. During biosynthesis of amphotericin, the macrolactone core undergoes three modifications: oxidation of a methyl branch to a carboxyl group, mycosaminylation, and hydroxylation. Gene disruption was undertaken to block two of these modifications. Initial experiments targeted the amphDIII gene, which encodes a GDP-D-mannose 4,6-dehydratase involved in biosynthesis of mycosamine. Analysis of products by mass spectrometry and NMR indicated that the amphDIII mutant produced 8-deoxyamphoteronolides A and B. This suggests that glycosylation with mycosamine normally precedes C-8 hydroxylation and that formation of the exocyclic carboxyl group can occur prior to both these modifications. Inactivation of the amphL cytochrome P450 gene led to production of novel polyenes with masses appropriate for 8-deoxyamphotericins A and B. These compounds retained antifungal activity and may be useful new antibiotics.
Other Sponsorship
European Union
Type of Material
Journal Article
Publisher
Elsevier
Journal
Chemistry and Biology
Volume
10
Issue
12
Start Page
1215
End Page
1224
Copyright (Published Version)
2003 Elsevier
Language
English
Status of Item
Peer reviewed
ISSN
1074-5521
This item is made available under a Creative Commons License
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