Biosynthesis of the polyene macrolide antibiotic nystatin in Streptomyces noursei

  title={Biosynthesis of the polyene macrolide antibiotic nystatin in Streptomyces noursei},
  author={Espen Fj{\ae}rvik and Sergey B. Zotchev},
  journal={Applied Microbiology and Biotechnology},
  • Espen Fjærvik, S. Zotchev
  • Published 8 February 2005
  • Biology, Chemistry, Engineering
  • Applied Microbiology and Biotechnology
The polyene macrolide antibiotic nystatin, produced commercially by the bacterium Streptomyces noursei, is an important antifungal agent used in human therapy for treatment of certain types of mycoses. Early studies on nystatin biosynthesis in S. noursei provided important information regarding the precursors utilised in nystatin biosynthesis and factors affecting antibiotic yield. New insights into the enzymology of nystatin synthesis became available after the gene cluster governing nystatin… 

Post-PKS modifications in the biosynthesis of the antifungal antibiotic nystatin.

The nystatin biosynthesis gene cluster of Streptomyces noursei has been cloned and sequenced, and the resulting mutants were shown to produce 16-decarboxy-16-methylnystatin, supporting the suggested biological role of NysN as C16 methyl oxidase.

Biosynthesis and pathway engineering of antifungal polyene macrolides in actinomycetes

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Substantial improvement of tetraene macrolide production in Streptomyces diastatochromogenes by cumulative drug resistance mutations

C cumulative drug-resistance mutation was used to obtain a quintuple mutant G5-59 with huge tetraene macrolide overproduction from the starting strain Streptomyces diastatochromogenes 1628, which could be useful for further improvement of tetraenes macrolides production at industrial level.

Biosynthetic engineering of polyene macrolides towards generation of improved antifungal and antiparasitic agents.

The biosynthetic approach is already yielding sufficient material for testing the toxicity and activity of new compounds, thus opening possibilities for discovery of leads for development of effective and safe antifungal and antiparasitic agents.

Characterization of the biosynthetic gene cluster of the polyene macrolide antibiotic reedsmycins from a marine-derived Streptomyces strain

Biosynthesis of RDM A is accomplished on a linear assembly line catalyzed by Rdm PKSs harboring a unique AT0 under the control of a complex regulatory system, which enables generation of new biologically active RDM derivatives at high yield and with improved properties by engineered biosynthesis.

Characterization of the P450 Monooxygenase NysL, Responsible for C-10 Hydroxylation during Biosynthesis of the Polyene Macrolide Antibiotic Nystatin in Streptomyces noursei

Results obtained clearly demonstrated that NysL is a hydroxylase responsible for the post-polyketide synthase modification of 10-deoxynystatin at position C-10, thereby providing new opportunities for engineered biosynthesis of novel nyStatin analogues hydroxymated at alternative positions of the macrolactone ring.

Actinomycete-Derived Polyketides as a Source of Antibiotics and Lead Structures for the Development of New Antimicrobial Drugs

This review covers the most relevant actinomycetes-derived polyketide drugs with antimicrobial activity, including anti-fungal agents and provides an overview of the source of the compounds, structure of the molecules, the biosynthetic principle, bioactivity and mechanisms of action, and the current stage of development.

Identification of a bioactive 51-membered macrolide complex by activation of a silent polyketide synthase in Streptomyces ambofaciens

There is a constant need for new and improved drugs to combat infectious diseases, cancer, and other major life-threatening conditions. The recent development of genomics-guided approaches for novel



Chemical Diversity of Polyene Macrolides Produced by Streptomyces noursei ATCC 11455 and Recombinant Strain ERD44 with Genetically Altered Polyketide Synthase NysC

Nystatin analogues with an expanded macrolactone ring were observed in the extract of the ERD44 mutant, suggesting that the altered PKS can “stutter” during the polyketide chain assembly.

Candicidin biosynthesis in Streptomyces griseus

The modular architecture of the candicidin PKS and the availability of the PKSs involved in the biosynthesis of three polyene antibiotics shall make possible the creation of new, less toxic and more active polyenes antibiotics through combinatorial biosynthesis and targeted mutagenesis.

Polyene antibiotic biosynthesis gene clusters

Successful genetic manipulation of the producing organisms leading to production of polyene analogues indicates good prospects for generating improved antifungal compounds via genetic engineering.

Production of polyene macrolide antibiotics.