Engineered Biosynthesis of Disaccharide-Modified Polyene Macrolides

Poire, Eimear De; Stephens, Niamh; Rawlings, Bernard J.; Caffrey, Patrick

doi:10.1128/aem.02197-13

Cited by 17 publications

(26 citation statements)

References 26 publications

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“…NypY did not act on nystatins in S. noursei (Seipke et al, 2012) but in S. nodosus showed modest activity towards amphotericins A and B (De Poire et al, 2013). Slightly more efficient modification of 7-keto amphotericin B was observed in the S. nodosus KR16 mutant.…”

Section: Extending Glycosyltransferasesmentioning

confidence: 90%

“…In nystatin, the C35 hydroxyl group may be modified with L-digitoxose or L-mycarose sugars (Bruheim et al, 2004). For a few polyenes, the mycosaminyl residue is modified with a second sugar to form a disaccharide chain (De Poire et al, 2013). The p-aminobenzoyl moiety of some aromatic heptaenes is N-methylated (see below).…”

Section: Genes For Polyene Macrolide Biosynthesismentioning

confidence: 99%

“…The extending GT gene pegA was not within the main cluster but was apparently located within a transposable element. Heterologous expression in other polyene producers revealed that the enzyme did not act on amphotericins but showed weak activity towards candicidins, which are more similar to the natural acceptor substrate (De Poire et al, 2013). PegA shows about 48% sequence identity with AmphDI, suggesting that extending GTs and mycosaminyltransferases have a close evolutionary relationship.…”

Section: Extending Glycosyltransferasesmentioning

confidence: 99%

See 2 more Smart Citations

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: Extending Glycosyltransferasesmentioning

confidence: 90%

Section: Genes For Polyene Macrolide Biosynthesismentioning

confidence: 99%

Section: Extending Glycosyltransferasesmentioning

confidence: 99%

See 1 more Smart Citation

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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“…The pegA gene from A. caeruleus was expressed in Streptomyces albidoflavus, producer of candicidins, aromatic heptaenes similar in structure to 67-121A. This resulted in formation of small amounts of mannosyl candicidins (De Poire et al, 2013). On this evidence, PegA was identified as the extending glycosyltransferase that forms 67-121C (Fig.…”

Section: C From Actinoplanes Caeruleus Dsm43634 Npp (Nystatin-likmentioning

confidence: 99%

“…The putative 7-oxo disaccharide analogues were detected by LC-MS but were minor components relative to the normal monosaccharide polyenes. Because of the low yields, none of these new compounds was purified and characterised further (De Poire et al, 2013). Larger amounts of disaccharide-modified polyenes are required for purification, structure analysis, and assessment of biological activities.…”

Section: C From Actinoplanes Caeruleus Dsm43634 Npp (Nystatin-likmentioning

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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Improvement of amphotericin B production by a newly isolated Streptomyces nodosus mutant

Zhang

Zhou

et al. 2017

Biotech and App Biochem

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Amphotericin B is an effective antifungal antibiotic. However, its production in the wild-type strain of Streptomyces nodosus is relatively low. In this study, a strain of ZJB 20130827, capable of producing amphotericin B, was isolated and identified as S. nodosus based on its physiological and biochemical characteristics as well as its 16S rRNA gene sequence analysis. With N-methyl-N-nitroso-N'-nitroguanidine (NTG) and ultraviolet (UV) treatment, this wild-type strain was mutated for improving the yield of amphotericin B. After NTG and UV treatment, the best mutant N3 was obtained for optimization of fermentation conditions. The production of amphotericin B with N3 was 5,260 mg/L, while the wild-type strain ZJB 20130827 was about 580 mg/L, an increase of 906.9%. A genetically stable mutant strain with high yield of amphotericin B was obtained using NTG and UV. The mutant obtained in this work could potentially be utilized in industrial production of amphotericin B.

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Engineered Biosynthesis of Disaccharide-Modified Polyene Macrolides

Cited by 17 publications

References 26 publications

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

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

Engineered biosynthesis and characterisation of disaccharide-modified 8-deoxyamphoteronolides

Improvement of amphotericin B production by a newly isolated Streptomyces nodosus mutant

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