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Phosphomannose isomerase and phosphomannomutase gene disruptions in Streptomyces nodosus: impact on amphotericin biosynthesis and implications for glycosylation engineering
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File | Description | Size | Format | |
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LNMetabEngRevised.pdf | 533.14 KB |
Author(s)
Date Issued
January 2009
Date Available
20T13:54:49Z January 2017
Abstract
Streptomycetes synthesise several bioactive natural products that are modified with sugar residues derived from GDP-mannose. These include the antifungal polyenes, the antibacterial antibiotics hygromycin A and mannopeptimycins, and the anticancer agent bleomycin. Three enzymes function in biosynthesis of GDP-mannose from the glycolytic intermediate fructose 6-phosphate: phosphomannose isomerase (PMI), phosphomannomutase (PMM) and GDP-mannose pyrophosphorylase (GMPP). Synthesis of GDP-mannose from exogenous mannose requires hexokinase or phosphotransferase enzymes together with PMM and GMPP. In this study, a region containing genes for PMI, PMM and GMPP was cloned from Streptomyces nodosus, producer of the polyenes amphotericins A and B. Inactivation of the manA gene for PMI resulted in production of amphotericins and their aglycones, 8-deoxyamphoteronolides. A double mutant lacking the PMI and PMM genes produced 8-deoxyamphoteronolides in good yields along with trace levels of glycosylated amphotericins. With further genetic engineering these mutants may activate alternative hexoses as GDP-sugars for transfer to aglycones in vivo.
Sponsorship
Higher Education Authority
University College Dublin
Type of Material
Journal Article
Publisher
Elsevier
Journal
Metabolic Engineering
Volume
11
Issue
1
Start Page
40
End Page
47
Copyright (Published Version)
2008 Elsevier
Language
English
Status of Item
Peer reviewed
This item is made available under a Creative Commons License
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