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Phosphomannose isomerase and phosphomannomutase gene disruptions in Streptomyces nodosus: Impact on amphotericin biosynthesis and implications for glycosylation engineering

Paper ID Volume ID Publish Year Pages File Format Full-Text
31847 44843 2009 8 PDF Available
Title
Phosphomannose isomerase and phosphomannomutase gene disruptions in Streptomyces nodosus: Impact on amphotericin biosynthesis and implications for glycosylation engineering
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.

Keywords
GDP-mannose biosynthesis; Polyenes; Natural productsESMS, electrospray mass spectrometry; GMPP, GDP-mannose pyrophosphorylase; GPDH, glucose-6-phosphate dehydrogenase; HK, hexokinase; ORF, open reading frame; PGI, phosphoglucose isomerase; PMI, phosphoman
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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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Publisher
Database: Elsevier - ScienceDirect
Journal: Metabolic Engineering - Volume 11, Issue 1, January 2009, Pages 40–47
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us