Phosphomannose isomerase and phosphomannomutase gene disruptions in Streptomyces nodosus: impact on amphotericin biosynthesis and implications for glycosylation engineering
|Title:||Phosphomannose isomerase and phosphomannomutase gene disruptions in Streptomyces nodosus: impact on amphotericin biosynthesis and implications for glycosylation engineering||Authors:||Nic Lochlain, Laura
|Permanent link:||http://hdl.handle.net/10197/8293||Date:||Jan-2009||Online since:||2017-01-20T13:54:49Z||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.||Funding Details:||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||Keywords:||GDP-mannose biosynthesis; Polyenes; Natural products||DOI:||10.1016/j.ymben.2008.08.007||Language:||en||Status of Item:||Peer reviewed|
|Appears in Collections:||Biomolecular and Biomedical Science Research Collection|
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