ArticleApplied and environmental microbiology2006
Characterization of the P450 monooxygenase NysL, responsible for C-10 hydroxylation during biosynthesis of the polyene macrolide antibiotic nystatin in Streptomyces noursei.
Article in Applied and environmental microbiology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 56 citations in OpenAlex.
- Modular biosynthesis of microbiome-derived polyketides and nonribosomal peptides: insights and opportunities for Lactobacillaceae.Microbial cell factories · 2026Review
- Research and Application of the Polyene Macrolide Antibiotic Nystatin.Molecules (Basel, Switzerland) · 2026Review
- Biosynthesis of reveromycin derivatives by altering the regioselectivity of cytochrome P450revI.Chemical science · 2025Article
- 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
- Whole-genome sequencing-based characterization ofAccess microbiology · 2023Article
- New Glycosylated Polyene Macrolides: Refining the Ore from Genome Mining.Antibiotics (Basel, Switzerland) · 2022Review
- Optimization of tetramycin production in Streptomyces ahygroscopicus S91.Journal of biological engineering · 2021Article
- Stimulated Biosynthesis of an C10-Deoxy Heptaene NPP B2Frontiers in microbiology · 2020Article
- Improved recovery and biological activities of an engineered polyene NPP analogue in Pseudonocardia autotrophica.Journal of industrial microbiology & biotechnology · 2017Article
- Cytochromes P450 for natural product biosynthesis in Streptomyces: sequence, structure, and function.Natural product reports · 2017Review
- Selvamicin, an atypical antifungal polyene from two alternative genomic contexts.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Biotechnological production and application of the antibiotic pimaricin: biosynthesis and its regulation.Applied microbiology and biotechnology · 2016Review
- Article
- Post-PKS tailoring steps of a disaccharide-containing polyene NPP in Pseudonocardia autotrophica.PloS one · 2015Article
- Biosynthesis and pathway engineering of antifungal polyene macrolides in actinomycetes.Journal of industrial microbiology & biotechnology · 2013Review
- New nystatin-related antifungal polyene macrolides with altered polyol region generated via biosynthetic engineering of Streptomyces noursei.Applied and environmental microbiology · 2011Article
- Structure of cytochrome P450 PimD suggests epoxidation of the polyene macrolide pimaricin occurs via a hydroperoxoferric intermediate.Chemistry & biology · 2010Article
- The in vitro characterization of polyene glycosyltransferases AmphDI and NysDI.Chembiochem : a European journal of chemical biology · 2008Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The nysL gene, encoding a putative P450 monooxygenase, was identified in the nystatin biosynthetic gene cluster of Streptomyces noursei. Although it has been proposed that NysL is responsible for hydroxylation of the nystatin precursor, experimental evidence for this activity was lacking. The nysL gene was inactivated in S. noursei by gene replacement, and the resulting mutant was shown to produce 10-deoxynystatin. Purification and an in vitro activity assay for 10-deoxynystatin demonstrated its antifungal activity being equal to that of nystatin. The NysL protein was expressed heterologously in Escherichia coli as a His-tagged protein and used in an enzyme assay with 10-deoxynystatin as a substrate. The results obtained clearly demonstrated that NysL is a hydroxylase responsible for the post-polyketide synthase modification of 10-deoxynystatin at position C-10. Kinetic studies with the purified recombinant enzyme allowed determination of K(m) and k(cat) and revealed no inhibition of recombinant NysL by either the substrate or the product. These studies open the possibility for in vitro evolution of NysL aimed at changing its specificity, thereby providing new opportunities for engineered biosynthesis of novel nystatin analogues hydroxylated at alternative positions of the macrolactone ring.
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