ArticlePloS one2015
Post-PKS tailoring steps of a disaccharide-containing polyene NPP in Pseudonocardia autotrophica.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 20 citations in OpenAlex.
- Engineered biosynthesis and characterization of disaccharide-pimaricin.Microbial cell factories · 2025Article
- Effect of Post-Polyketide Synthase Modification Groups on Property and Activity of Polyene Macrolides.Antibiotics (Basel, Switzerland) · 2023Review
- Polyenic Antibiotics and Other Antifungal Compounds Produced by HemolyticInternational journal of molecular sciences · 2022Review
- Article
- New Glycosylated Polyene Macrolides: Refining the Ore from Genome Mining.Antibiotics (Basel, Switzerland) · 2022Review
- BAC cloning and heterologous expression of a giant biosynthetic gene cluster encoding antifungal neotetrafibricin inFrontiers in bioengineering and biotechnology · 2022Article
- Stimulated Biosynthesis of an C10-Deoxy Heptaene NPP B2Frontiers in microbiology · 2020Article
- Pseudonocardia strain improvement for stimulation of the di-sugar heptaene Nystatin-like Pseudonocardia polyene B1 biosynthesis.Journal of industrial microbiology & biotechnology · 2019Article
- Nystatin-like Pseudonocardia polyene B1, a novel disaccharide-containing antifungal heptaene antibiotic.Scientific reports · 2018Article
- Improved recovery and biological activities of an engineered polyene NPP analogue in Pseudonocardia autotrophica.Journal of industrial microbiology & biotechnology · 2017Article
- Carboxyl-terminal domain characterization of polyene-specific P450 hydroxylase in Pseudonocardia autotrophica.Journal of industrial microbiology & biotechnology · 2016Article
- Genome Analysis of TwoFrontiers in microbiology · 2016Article
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6 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
A novel polyene compound NPP identified in a rare actinomycetes, Pseudonocardia autotrophica KCTC9441, was shown to contain an aglycone identical to nystatin but to harbor a unique di-sugar moiety, mycosaminyl-(α1-4)-N-acetyl-glucosamine, which led to higher solubility and reduced hemolytic activity. Although the nppDI was proved to be responsible for the transfer of first polyene sugar, mycosamine in NPP biosynthesis, the gene responsible for the second sugar extending glycosyltransferase (GT) as well as NPP post-PKS tailoring mechanism remained unknown. Here, we identified a NPP-specific second sugar extending GT gene named nppY, located at the edge of the NPP biosynthetic gene cluster. Targeted nppY gene deletion and its complementation proved that nppY is indeed responsible for the transfer of second sugar, N-acetyl-glucosamine in NPP biosynthesis. Site-directed mutagenesis on nppY also revealed several amino acid residues critical for NppY GT function. Moreover, a combination of deletions and complementations of two GT genes (nppDI and nppY) and one P450 hydroxylase gene (nppL) involved in the NPP post-PKS biosynthesis revealed that NPP aglycone is sequentially modified by the two different GTs encoded by nppDI and nppY, respectively, followed by the nppL-driven regio-specific hydroxylation at the NPP C10 position. These results set the stage for the biotechnological application of sugar diversification for the biosynthesis of novel polyene compounds in actinomycetes.
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