Engineered biosynthesis and characterisation of disaccharide-modified 8-deoxyamphoteronolides

Walmsley, Simon; Poire, Eimear De; Rawlings, Bernard J.; Caffrey, Patrick

doi:10.1007/s00253-016-7986-6

Cited by 8 publications

(8 citation statements)

References 30 publications

(37 reference statements)

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“…Accordingly, Ae707_Ps1 and all the Ps1 strains encode an additional glycosyl transferase. Heterologous expression of nypY in the amphotericin producer Streptomyces nodosus led to a new amphotericin derivative with D -mannose attached to the D -mycosamine via a β-1,4-linkage (Walmsley et al, 2016). We therefore predict the same modification leading to the product shown in Figure 7 , and that this is identical to nystatin P1.…”

Section: Resultsmentioning

confidence: 99%

Genome Analysis of Two Pseudonocardia Phylotypes Associated with Acromyrmex Leafcutter Ants Reveals Their Biosynthetic Potential

et al. 2016

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The attine ants of South and Central America are ancient farmers, having evolved a symbiosis with a fungal food crop >50 million years ago. The most evolutionarily derived attines are the Atta and Acromyrmex leafcutter ants, which harvest fresh leaves to feed their fungus. Acromyrmex and many other attines vertically transmit a mutualistic strain of Pseudonocardia and use antifungal compounds made by these bacteria to protect their fungal partner against co-evolved fungal pathogens of the genus Escovopsis. Pseudonocardia mutualists associated with the attines Apterostigma dentigerum and Trachymyrmex cornetzi make novel cyclic depsipeptide compounds called gerumycins, while a mutualist strain isolated from derived Acromyrmex octospinosus makes an unusual polyene antifungal called nystatin P1. The novelty of these antimicrobials suggests there is merit in exploring secondary metabolites of Pseudonocardia on a genome-wide scale. Here, we report a genomic analysis of the Pseudonocardia phylotypes Ps1 and Ps2 that are consistently associated with Acromyrmex ants collected in Gamboa, Panama. These were previously distinguished solely on the basis of 16S rRNA gene sequencing but genome sequencing of five Ps1 and five Ps2 strains revealed that the phylotypes are distinct species and each encodes between 11 and 15 secondary metabolite biosynthetic gene clusters (BGCs). There are signature BGCs for Ps1 and Ps2 strains and some that are conserved in both. Ps1 strains all contain BGCs encoding nystatin P1-like antifungals, while the Ps2 strains encode novel nystatin-like molecules. Strains show variations in the arrangement of these BGCs that resemble those seen in gerumycin gene clusters. Genome analyses and invasion assays support our hypothesis that vertically transmitted Ps1 and Ps2 strains have antibacterial activity that could help shape the cuticular microbiome. Thus, our work defines the Pseudonocardia species associated with Acromyrmex ants and supports the hypothesis that Pseudonocardia species could provide a valuable source of new antimicrobials.

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Section: Resultsmentioning

confidence: 99%

Genome Analysis of Two Pseudonocardia Phylotypes Associated with Acromyrmex Leafcutter Ants Reveals Their Biosynthetic Potential

et al. 2016

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“…P1 NypY GT is also discriminating, showing a preference for 8-deoxyamphotericins over amphotericins. 45 With aromatic heptaenes there is no cytochrome P450-mediated hydroxylation of the polyol chain. In 67-121C biosynthesis, the specificity of the ABC transporters may ensure that all late modifications are complete before export occurs.…”

Section: Discussionmentioning

confidence: 99%

New insights into polyene macrolide biosynthesis in Couchioplanes caeruleus

2017

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Couchioplanes caeruleus DSM43634 synthesises 67-121C, an aromatic heptaene macrolide that contains a mannosyl-mycosaminyl disaccharide. An improved draft genome sequence was used to obtain the biosynthetic gene cluster for this antifungal. Bioinformatic analysis of the polyketide synthase indicated that extension modules 7 and 8 contain A-type ketoreductase and dehydratase domains. These modules are therefore predicted to form cis double bonds. The deduced stereostructure of the 67-121C macrolactone is identical to that experimentally determined for the partricin subgroup of aromatic heptaenes. Some of these polyenes are N-methylated on the aminoacetophenone moiety. The C. caeruleus AceS protein was shown to methylate 4-aminoacetophenone and esters of 4-aminobenzoate, but not 4-aminobenzoate. This suggests that the substrate specificity of AceS prevents it from interfering with folate biosynthesis. The methyltransferase should be valuable for chemoenzymatic alkylation of compounds that contain aminobenzoyl moieties.

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“…例如, 将基因nppY导入两性霉素产生菌S. nodosus, KR16结构域失活或基因amphL缺失菌株, 可以分别产生4′-甘露糖两性霉素B(24) [54] 、7-酮基-4′-甘露糖两性霉素 B(25) [54] 及 8-去羟基 -4′-甘露糖两性霉素 B(26) [31] . 此外, NppY及其同源蛋白PegA [55] 还可以将杀念菌素/抗生素FR-008 III转化为4′-甘露糖衍生物 27 [54] (图4).…”

Section: 除单糖多烯大环内酯抗生素外越来越多的新unclassified

Structural modifications and yield improvements of polyene macrolide antibiotics

Qi¹,

LinQuan²

2017

Chin. Sci. Bull.

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Engineered biosynthesis and characterisation of disaccharide-modified 8-deoxyamphoteronolides

Cited by 8 publications

References 30 publications

Genome Analysis of Two Pseudonocardia Phylotypes Associated with Acromyrmex Leafcutter Ants Reveals Their Biosynthetic Potential

Genome Analysis of Two Pseudonocardia Phylotypes Associated with Acromyrmex Leafcutter Ants Reveals Their Biosynthetic Potential

New insights into polyene macrolide biosynthesis in Couchioplanes caeruleus

Structural modifications and yield improvements of polyene macrolide antibiotics

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