Versatility of Enzymes Catalyzing Late Steps in Polyene 67-121C Biosynthesis

Stephens, Niamh; Rawlings, Bernard J.; Caffrey, Patrick

doi:10.1271/bbb.120961

Cited by 13 publications

(18 citation statements)

References 22 publications

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“…In contrast, two GTs that normally act on aromatic heptaenes do not recognise amphotericin aglycones in vivo. These are the PerDI perosaminyltransferase from S. cacaoi and the AceDI mycosaminyltransferase from A. caeruleus (Hutchinson et al, 2010;Stephens et al, 2013). These enzymes appear to have a lower tolerance for unnatural acceptors.…”

Section: Glycosylationmentioning

confidence: 99%

Polyene macrolide biosynthesis in streptomycetes and related bacteria: recent advances from genome sequencing and experimental studies

Caffrey

Poire

Sheehan

et al. 2016

Appl Microbiol Biotechnol

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Section: Glycosylationmentioning

confidence: 99%

Polyene macrolide biosynthesis in streptomycetes and related bacteria: recent advances from genome sequencing and experimental studies

Caffrey

Poire

Sheehan

et al. 2016

Appl Microbiol Biotechnol

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“…3). This was predicted from the high sequence homology between 6 NypY and known inverting polyene glycosyltransferases (PegA, AmphDI and NysDI) that use GDP--Dmannose or GDP--D-mycosamine Stephens et al, 2013;De Poire et al, 2013).…”

Section: Purification Of Mannosyl-8-deoxyamphotericin B and Structuramentioning

confidence: 99%

Engineered biosynthesis and characterisation of disaccharide-modified 8-deoxyamphoteronolides

Walmsley

Poire

Rawlings

et al. 2016

Appl Microbiol Biotechnol

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Several polyene macrolides are potent antifungal agents that have severe side effects. Increased glycosylation of these compounds can improve water-solubility and reduce toxicity. Three extending glycosyltransferases are known to add hexoses to the mycosaminyl sugar residues of polyenes. The adds an extra hexose to a nystatin but the identity of the sugar is unknown. Here we express the nypY gene in Streptomyces nodosus amphL and show that NypY modifies 8-deoxyamphotericins more efficiently than C-8 hydroxylated forms. The modified heptaene was purified and shown to be mannosyl-8-deoxyamphotericin B. Actinoplanes caeruleusThis had the same antifungal activity as amphotericin B, but was slightly less haemolytic. Chemical modification of this new disaccharide polyene could give better antifungal antibiotics.

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“…The candicidin producer S. albidoflavus DSM40624 was transformed with the pIAGO-pegA1 (20) and pIAGO-nypY plasmids. The transformants were cultured, and polyenes were extracted into methanol by the same procedures used for amphotericins.…”

Section: S Nodosus Strain Nm Synthesizes 16-descarboxyl-16-methyl-ammentioning

confidence: 99%

“…Recently, we carried out draft genome sequencing of this organism and identified 67-121 late biosynthetic genes. The pegA gene for the extending glycosyltransferase was expressed in Streptomyces nodosus, but only trace amounts of mannosyl-amphotericins were produced (20). It was not possible to determine whether this was due to inefficient recognition of amphotericins by PegA, low intracellular levels of GDP-D-mannose, rapid export of amphotericins before mannosylation could occur, or other unknown limiting factors.…”

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confidence: 99%