Biosynthesis of Deoxyamphotericins and Deoxyamphoteronolides by Engineered Strains of Streptomyces nodosus

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Title: Biosynthesis of Deoxyamphotericins and Deoxyamphoteronolides by Engineered Strains of Streptomyces nodosus
Authors: Byrne, Barry
Carmody, Maria
Gibson, Emma
Rawlings, Bernard
Caffrey, Patrick
Permanent link: http://hdl.handle.net/10197/10037
Date: 19-Dec-2003
Online since: 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.
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
Keywords: Amphotericin BAntifungal antibioticStreptomyces nodosusAmphL cytochrome P450 gene
DOI: 10.1016/j.chembiol.2003.12.001
Language: en
Status of Item: Peer reviewed
Appears in Collections:Biomolecular and Biomedical Science Research Collection

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